US20030077227A1 - Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system - Google Patents

Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system Download PDF

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Publication number
US20030077227A1
US20030077227A1 US10/230,060 US23006002A US2003077227A1 US 20030077227 A1 US20030077227 A1 US 20030077227A1 US 23006002 A US23006002 A US 23006002A US 2003077227 A1 US2003077227 A1 US 2003077227A1
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United States
Prior art keywords
composition
active compound
mixtures
group
percent
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
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US10/230,060
Inventor
Harry Dugger
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Flemington Pharmaceutical Corp
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Flemington Pharmaceutical Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Priority claimed from PCT/US1997/017899 external-priority patent/WO1999016417A1/en
Priority to US10/230,060 priority Critical patent/US20030077227A1/en
Application filed by Flemington Pharmaceutical Corp filed Critical Flemington Pharmaceutical Corp
Assigned to NOVADEL PHARMA INC. reassignment NOVADEL PHARMA INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DUGGER, HARRY A. III
Publication of US20030077227A1 publication Critical patent/US20030077227A1/en
Priority to JP2004545251A priority patent/JP2006505569A/en
Priority to CA002497262A priority patent/CA2497262A1/en
Priority to EP10181746A priority patent/EP2277506A1/en
Priority to EP10181730A priority patent/EP2283815A1/en
Priority to EP03796314A priority patent/EP1539106A2/en
Priority to EP10181677A priority patent/EP2283813B1/en
Priority to AU2003298564A priority patent/AU2003298564A1/en
Priority to EP10181701A priority patent/EP2283814B1/en
Priority to PCT/US2003/026847 priority patent/WO2004035021A2/en
Priority to US10/671,715 priority patent/US7632517B2/en
Priority to US10/671,709 priority patent/US20050163719A1/en
Priority to US10/671,720 priority patent/US20040141923A1/en
Priority to US10/726,585 priority patent/US6977070B2/en
Priority to US10/834,815 priority patent/US20050002867A1/en
Priority to US11/384,444 priority patent/US20060159624A1/en
Priority to US11/391,297 priority patent/US20060171896A1/en
Priority to US11/442,137 priority patent/US20060222597A1/en
Priority to US11/443,254 priority patent/US20060216241A1/en
Priority to US11/443,253 priority patent/US20060216240A1/en
Assigned to PROQUEST INVESTMENTS III, L.P. AS COLLATERAL AGENT FOR SECURED PARTIES reassignment PROQUEST INVESTMENTS III, L.P. AS COLLATERAL AGENT FOR SECURED PARTIES SECURITY AGREEMENT Assignors: NOVADEL PHARMA INC.
Priority to US12/350,915 priority patent/US20090131514A1/en
Priority to US12/351,275 priority patent/US20090186099A1/en
Priority to US12/394,903 priority patent/US20090162300A1/en
Priority to US12/576,457 priority patent/US8236285B2/en
Assigned to NOVADEL PHARMA INC. reassignment NOVADEL PHARMA INC. RELEASE BY SECURED PARTY (SEE DOCUMENT FOR DETAILS). Assignors: PROQUEST INVESTMENTS III, L.P. AS COLLATERAL AGENT
Priority to US13/208,429 priority patent/US20110293536A1/en
Priority to US16/130,860 priority patent/US20190083471A1/en
Priority to US16/665,622 priority patent/US20200061034A1/en
Abandoned legal-status Critical Current

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Definitions

  • Aerosol compositions containing a hydrocarbon propellant and a drug for administration to a mucosal surface are described in U.K. 2,082,457, Su, U.S. Pat. No. 3,155,574, Silson et al., U.S. Pat. No. 5,011,678, Wang et al., and by Parnell in U.S. Pat. No. 5,128,132. It should be noted that these references discuss bioavailability of solutions by inhalation rather than through the membranes to which they are administered.
  • a buccal aerosol spray or soft bite gelatin capsule using a polar or non-polar solvent has now been developed which provides biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect.
  • the composition comprises: propellant 10-70%, non-polar solvent 25-89.9%, active compound 0.01-40%, flavoring agent 1-8%; most suitably propellant 20-70%, non-polar solvent 25-74.75%, active compound 0.25-35%, flavoring agent 2-7.5%.
  • compositions of the present invention for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent are also administrable in aerosol form driven by a propellant.
  • the composition comprises in weight % of total composition: aqueous polar solvent 10-97%, active compound 0.1-25%, suitably additionally comprising, by weight of total composition a flavoring agent 0.05-10% and propellant: 2-10%.
  • the composition comprises: polar solvent 20-97%, active compound 0.1-15%, flavoring agent 0.1-5% and propellant 2-5%; most suitably polar solvent 25-97%, active compound 0.2-25%, flavoring agent 0.1-2.5% and propellant 2-4%.
  • the buccal pump spray composition of the present invention i.e., the propellant free composition, for transmucosal administration of a pharmacologically active compound wherein said active compound is soluble in a pharmacologically acceptable non-polar solvent comprises in weight % of total composition: non-polar solvent 30-99.69%, active compound 0.005-55%, and suitably additionally, flavoring agent 0.1-10%.
  • the composition comprises: polar solvent 37-98.58%, active compound 0.005-55%, flavoring agent 0.5-8%; most suitably polar solvent 60.9-97.06%, active compound 0.01-40%, flavoring agent 0.75-7.5%.
  • the soft bite gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable non-polar solvent, having charged thereto a fill composition comprise in weight % of total composition: non-polar solvent 4-99.99%, emulsifier 0-20%, active compound 0.01-80%, provided that said fill composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 0.01-10%.
  • the soft bite gelatin capsule comprises: non-polar solvent 21.5-99.975%, emulsifier 0-15%, active compound 0.025-70%, flavoring agent 1-8%; most suitably: nonpolar solvent 28.5-97.9%, emulsifier 0-10%, active compound 0.1-65.0%, flavoring agent 2-6%.
  • the soft bite gelatin capsule comprises: polar solvent 37-99.95%, emulsifier 0-15%, active compound 0.025-55%, flavoring agent 1-8%; most suitably: polar solvent 44-96.925%, emulsifier 0-10%, active compound 0.075-50%, flavoring agent 2-6%.
  • a further object is a sealed aerosol spray container containing a composition of the non polar or polar aerosol spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.
  • the propellant is a non-Freon material, preferably a C 3-8 hydrocarbon of a linear or branched configuration.
  • the propellant should be substantially non-aqueous.
  • the propellant produces a pressure in the aerosol container such that under expected normal usage it will produce sufficient pressure to expel the solvent from the container when the valve is activated but not excessive pressure such as to damage the container or valve seals.
  • the non-polar solvent is a non-polar hydrocarbon, preferably a C 7-18 hydrocarbon of a linear or branched configuration, fatty acid esters, and triglycerides, such as miglyol.
  • the solvent must dissolve the active compound and be miscible with the propellant, i.e., solvent and propellant must form a single phase at a temperature of 0-40° C. a pressure range of between 1-3 atm.
  • the polar and non-polar aerosol spray compositions of the invention are intended to be administered from a sealed, pressurized container. Unlike a pump spray, which allows the entry of air into the container after every activation, the aerosol container of the invention is sealed at the time of manufacture. The contents of the container are released by activation of a metered valve, which does not allow entry of atmospheric gasses with each activation.
  • a metered valve which does not allow entry of atmospheric gasses with each activation.
  • a further object is a pump spray container containing a composition of the pump spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.
  • a further object is a soft gelatin bite capsule containing a composition of as set forth above.
  • the formulation may be in the form of a viscous solution or paste containing the active compounds. Although solutions are preferred, paste fills may also be used where the active compound is not soluble or only partially soluble in the solvent of choice. Where water is used to form part of the paste composition, it should not exceed 10% thereof. (All percentages herein are by weight unless otherwise indicated.)
  • the polar or non-polar solvent is chosen such that it is compatible with the gelatin shell and the active compound.
  • the solvent preferably dissolves the active compound.
  • other components wherein the active compound is not soluble or only slightly soluble may be used and will form a paste fill.
  • Soft gelatin capsules are well known in the art. See, for example, U.S. Pat. No. 4,935,243, Borkan et al., for its teaching of such capsules.
  • the capsules of the present invention are intended to be bitten into to release the low viscosity solution or paste therein, which will then coat the buccal mucosa with the active compounds.
  • the shell of a soft gelatin capsule of the invention may comprise, for example: gelatin: 50-75%, glycerin 20-30%, colorants 0.5-1.5%, water 5-10%, and sorbitol 2-10%.
  • the active compound may include, biologically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostaglandins and neutraceuticals.
  • the active compounds may also include antihistamines, alkaloids, hormones, benzodiazepines and narcotic analgesics. While not limited thereto, these active compounds are particularly suitable for non-polar pump spray formulation and application.
  • the active compounds may also include p-FOX (fatty acid oxidation) inhibitors, acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, or a mixture thereof.
  • p-FOX fatty acid oxidation
  • FIG. 1. is a schematic diagram showing routes of absorption and processing of pharmacologically active substances in a mammalian system.
  • the preferred active compounds of the present invention are in an ionized, salt form or as the free base of the pharmaceutically acceptable salts thereof (provided, for the aerosol or pump spray compositions, they are soluble in the spray solvent). These compounds are soluble in the non-polar solvents of the invention at useful concentrations or can be prepared as pastes at useful concentrations. These concentrations may be less than the standard accepted dose for these compounds since there is enhanced absorption of the compounds through the oral mucosa. This aspect of the invention is especially important when there is a large (40-99.99%) first pass effect.
  • propellants for the non polar sprays propane, N-butane, iso-butane, N-pentane, iso-pentane, and neo-pentane, and mixtures thereof may be used.
  • N-butane and iso-butane, as single gases, are the preferred propellants. It is permissible for the propellant to have a water content of no more than 0.2%, typically 0.1-0.2%. All percentages herein are by weight unless otherwise indicated. It is also preferable that the propellant be synthetically produced to minimize the presence of contaminants which are harmful to the active compounds. These contaminants include oxidizing agents, reducing agents, Lewis acids or bases, and water. The concentration of each of these should be less than 0.1%, except that water may be as high as 0.2%.
  • Suitable non-polar solvents for the capsules and the non-polar sprays include (C 2 -C 24 ) fatty acid (C 2 -C 6 ) esters, C 7 -C 18 hydrocarbon, C 2 -C 6 alkanoyl esters, and the triglycerides of the corresponding acids.
  • other liquid components may be used instead of the above low molecular weight solvents. These include soya oil, corn oil, other vegetable oils.
  • solvents for the polar capsules or sprays there may be used low molecular weight polyethyleneglycols (PEG) of 400-1000 Mw (preferably 400-600), low molecular weight (C 2 -C 8 ) mono and polyols and alcohols of C 7 -C 18 linear or branch chain hydrocarbons, glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.
  • PEG polyethyleneglycols
  • C 2 -C 8 low molecular weight mono and polyols and alcohols of C 7 -C 18 linear or branch chain hydrocarbons
  • glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.
  • the preferred flavoring agents are synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners (sugars, aspartame, saccharin, etc.), and combinations thereof.
  • the active substances include the active compounds selected from the group consisting of cyclosporine, sermorelin, octreotide acetate, calcitonin-salmon, insulin lispro, sumatriptan succinate, clozepine, cyclobenzaprine, dexfenfluramine hydrochloride, glyburide, zidovudine, erythromycin, ciprofloxacin, ondansetron hydrochloride, dimenhydrinate, cimetidine hydrochloride, famotidine, phenytoin sodium, phenytoin, carboprost thromethamine, carboprost, diphenhydramine hydrochloride, isoproterenol hydrochloride, terbutaline sulfate, terbutaline, theophylline, albuterol sulfate and neutraceuticals, that is to say nutrients with pharmacological action such as but not limited to carnitine
  • the active compound is a p-FOX (fatty acid oxidation) inhibitor, acetylcholinesterase inhibitor, nerve impulse inhibitor, anti-cholinergic, anti-convulsant, anti-psychotic, anxiolytic agent, dopamine metabolism inhibitor, agent to treat post stroke sequelae, neuroprotectant, agent to treat Alzheimer's disease, neurotransmitter, neurotransmitter agonist, sedative, agent for treating attention deficit disorder, agent for treating narcolepsy, central adregenic antagonist, anti-depression agent, agent for treating Parkinson's disease, benzodiazepine antagonist, stimulant, neurotransmitter antagonist, tranquilizer, or a mixture thereof.
  • p-FOX fatty acid oxidation
  • the active compound is a p-FOX inhibitor.
  • a suitable p-FOX inhibitor for use in the buccal sprays of the invention includes, but is not limited to, ranolazine.
  • the active compound is an acetylcholinesterase inhibitor.
  • Suitable acetylcholinesterase inhibitors for use in the buccal sprays of the invention include, but are not limited to, galantamine, neostigmine, physostigmine, and edrophonium.
  • the active compound is a nerve impulse inhibitor.
  • Suitable nerve impulse inhibitors for use in the buccal sprays of the invention include, but are not limited to, levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, and rocuronium.
  • the active compound is an anti-cholinergic.
  • Suitable anti-cholinergics for use in the buccal sprays of the invention include, but are not limited to, amantadine, ipratropium, oxitropium, and dicycloverine.
  • the active compound is an anti-convulsant.
  • Suitable anti-convulsants for use in the buccal sprays of the invention include, but are not limited to, acetazolamide, carbamazepine, clonazepam, diazepam, divalproex (valproic acid), ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, and zonisamide.
  • the active compound is an anti-psychotic.
  • Suitable anti-psychotics for use in the buccal sprays of the invention include, but are not limited to, amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, and ziprasidone,
  • the active compound is an anxiolytic agent.
  • Suitable anxiolytic agents for use in the buccal sprays of the invention include, but are not limited to, amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, and zopiclone.
  • the active compound is a dopamine metabolism inhibitor.
  • Suitable dopamine metabolism inhibitors for use in the buccal sprays of the invention include, but are not limited to, entacapone, lazebemide, selegiline, and tolcapone.
  • the active compound is an agent to treat post stroke sequelae.
  • Suitable agents to treat post stroke sequelae for use in the buccal sprays of the invention include, but are not limited to, glatiramer, interferon beta 1A, interferon beta 1B, estradiol, and progesterone.
  • the active compound is a neuroprotectant.
  • Suitable neuroprotectants for use in the buccal sprays of the invention include, but are not limited to, donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, and xaliproden.
  • the active compound is an agent to treat Alzheimer's disease.
  • Suitable agents to treat Alzheimer's disease for use in the buccal sprays of the invention include, but are not limited to, carbidopa, levodopa, tacrine, donezepil, rivastigmine, and galantamine.
  • the active compound is a neurotransmitter.
  • Suitable neurotransmitters for use in the buccal sprays of the invention include, but are not limited to, acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, and nitric oxide.
  • the active compound is a neurotransmitter agonist.
  • Suitable neurotransmitter agonists for use in the buccal sprays of the invention include, but are not limited to, almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, traz
  • the active compound is a sedative.
  • Suitable sedatives for use in the buccal sprays of the invention include, but are not limited to, dexmedetomidine, eszopiclone, indiplon, zolpidem, and zaleplon.
  • the active compound is an agent for treating attention deficit disorder.
  • Suitable agents for treating attention deficit disorder for use in the buccal sprays of the invention include, but are not limited to, amphetamine, dextroamphetamine, methylphenidate, and pemoline.
  • the active compound is an agent for treating narcolepsy.
  • Suitable agents for treating narcolepsy for use in the buccal sprays of the invention include, but are not limited to, modafinil and mazindol.
  • the active compound is a central adregenic antagonists.
  • a suitable central adregenic antagonists for use in the buccal sprays of the invention includes, but is not limited to, mesoridazine.
  • the active compound is an anti-depression agent.
  • Suitable anti-depression agents for use in the buccal sprays of the invention include, but are not limited to, amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, and venlafaxine.
  • the active compound is an agent for treating Parkinson's disease.
  • Suitable agents for treating Parkinson's disease for use in the buccal sprays of the invention include, but are not limited to, amantadine, bromocriptine, carvidopa, levodopa, pergolide, and selegiline.
  • the active compound is a benzodiazepine antagonist.
  • a suitable benzodiazepine antagonist for use in the buccal sprays of the invention includes, but is not limited to, flumazenil.
  • the active compound is a neurotransmitter antagonist.
  • a suitable neurotransmitter antagonist for use in the buccal sprays of the invention includes, but is not limited, to deramciclane.
  • the active compound is a stimulant.
  • Suitable stimulants for use in the buccal sprays of the invention include, but are not limited to, amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, and pemoline.
  • the active compound is a tranquilizer.
  • a suitable tranquilizer for use in the buccal sprays of the invention includes, but is not limited to, mesoridazine.
  • compositions of the present invention comprise an active compound or a pharmaceutically acceptable salt thereof.
  • pharmaceutically acceptable salts refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases including organic and inorganic acids or bases.
  • salts may be prepared from pharmaceutically acceptable non-toxic bases.
  • Salts derived from all stable forms of inorganic bases include aluminum, ammonium, calcium, copper, iron, lithium, magnesium, manganese, potassium, sodium, zinc, etc. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts.
  • Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion-exchange resins such as arginine, betaine, caffeine, choline, N,N dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethyl-aminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, isopropylamine, lysine, methyl-glucosamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purine, theobromine, triethylamine, trimethylamine, tripropylamine, etc.
  • basic ion-exchange resins such as arginine, betaine, caffeine, choline
  • salts may be prepared from pharmaceutically acceptable non-toxic acids.
  • acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethane-sulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, etc.
  • Particularly preferred are citric, hydrobromic, maleic, phosphoric, sulfuric, and tartaric acids.
  • CNS active amines and their salts including but not limited to tricyclic amines, GABA analogues, thiazides, phenothiazine derivatives, serotonin antagonists and serotonin reuptake inhibitors
  • Sumatriptan succinate bite capsule Amounts preferred amount most preferred amount sumatriptan 0.01-5 0.05-3.5 0.075-1.75 succinate polyethylene 25-70 30-60 35-50 glycol glycerin 25-70 30-60 35-50 flavors 0.1-10 1-8 3-6 C.
  • Clozepine lingual spray Amounts preferred amount most preferred amount clozepine 0.5-30 1-20 10-15 ethanol 5-60 7.5-50 10-20 propylene 5-30 7.5-20 10-15 glycol polyethylene 0-60 30-45 35-40 glycol water 5-30 7.5-20 10-15 flavors 0.1-5 1-4 2-3 D.
  • Glyburide lingual spray Amounts preferred amount most preferred amount glyburide 0.25-25 0.5-20 0.75-15 ethanol 5-60 ⁇ 7.5-50 10-20 propylene 5-30 7.5-20 10-15 glycol polyethylene 0-60 30-45 35-40 glycol water 2.5-30 5-20 6-15 flavors 0.1-5 1-4 2-3
  • Glyburide non-polar bite capsule Amounts preferred amount most preferred amount glyburide 0.01-10 0.025-7.5 0.1-4 olive oil 30-60 35-55 30-50 polyoxyethylated oleic glycerides 30-60 35-55 30-50 flavors 0.1-5 1-4 2-3
  • Zidovudine (formerly called azidothymidine (AZT) (Retrovir)] non- polar lingual spray Amounts preferred amount most preferred amount zidovudine 10-50 15-40 25-35 Soya oil 20-85 25-70 30-40 Butane 15-80 30-75 60-70 flavors 0.1-5 1-4 2-3
  • Ciprofloxacin hydrochloride bite capsule Amounts preferred amount most preferred amount ciprofloxacin 25-65 35-55 40-50 hydrochloride glycerin 5-20 7.5-15 10-12.5 polyethylene 120-75 30-65 40-60 glycol flavors 1-10 2-8 3-6 D.
  • zidovudine [formerly called azidothymidine (AZT) (Retrovir] lingual spray Amounts preferred amount most preferred amount zidovudine 10-50 15-40 25-35 water 30-80 40-75 45-70 ethanol 5-20 7.5-15 9.5-12.5 polyethylene 5-20 7.5-15 9.5-12.5 glycol flavors 0.1-5 1-4 2-3
  • Ondansetron hydrochloride lingual spray Amounts preferred amount most preferred amount ondansetron 1-25 2-20 2.5-15 hydrochloride citric acid 1-10 2-8 2.5-5 monohydrate sodium citrate 0.5-5 1-4 1.25-2.5 dihydrate water 1-90 5-85 10-75 ethanol 5-30 7.5-20 9.5-15 propylene 5-30 7.5-20 9.5-15 glycol polyethylene 5-30 7.5-20 9.5-15 glycol flavors 1-10 3-8 5-7.5
  • Cimetidine hydrochloride bite capsule Amounts preferred amount most preferred amount cimetidine HCl 10-60 15-55 25-50 glycerin 5-20 7.5-15 10-12.5 polyethylene 20-90 25-85 30-75 glycol flavors 1-10 2-8 3-6
  • Famotidine lingual spray Amounts preferred amount most preferred amount famotidine 1-35 5-30 7-20 water 2.5-25 3-20 5-10 L-aspartic 0.1-20 1-15 5-10 acid polyethylene 20-97 30-95 50-85 glycol flavors 0.1-10 1-7.5 2-5 C.
  • Carboprost thromethamine lingual spray Amounts preferred amount most preferred amount carboprost 0.05-5 0.1-3 0.25-2.5 thromethamine water 50-95 60-80 65-75 ethanol 5-20 7.5-15 9.5-12.5 polyethylene 5-20 7.5-15 9.5-12.5 glycol sodium chloride 1-20 3-15 4-8 flavors 0.1-5 1-4 2-3 pH is adjusted with sodium hydroxide and/or hydrochloric acid B.
  • Echinacea as bite capsule Amounts preferred amount most preferred amount echinacea 30-85 40-75 45-55 extract soya oil 7.5-50 10-40 12.5-35 soya lecithin 0.001- 0.005-0.5 .01-0.1 1.0 Soya fats 7.5-50 10-40 12.5-35 flavors 1-10 2-8 3-6 D.
  • Diphenhydramine hydrochloride lingual spray Amounts preferred amount most preferred amount diphenhydramine 3-50. 4-40 5-35 HCl water 5-90 10-80 50-75 ethanol 1-80 3-50 5-10 polyethylene 1-80 3-50 5-15 glycol Sorbitol 0.1-5 0.2-4 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3
  • Theophylline polar bite capsule Amounts preferred amount most preferred amount theophylline 5-50 10-40 15-30 polyethylene 20-60 25-50 30-40 glycol glycerin 25-50 35-45 30-40 propylene 25-50 35-45 30-40 glycol flavors 0.1-5 1-4 2-3
  • Albuterol sulfate as polar lingual spray Amounts preferred amount most preferred amount albuterol 0.1-10 0.2-7.5 0.5-6 sulfate water 5-90 10-80 50-75 ethanol 1-10 2-8 2.5-5
  • Sorbitol 0.1-5 0.2-4 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3
  • Polar Solvent Formulations Using a Propellant A. Sulfonylurea Amount Preferred Amount Most-Preferred Amount glyburide 0.1-25% 0.5-15% 0.6-10% Ethanol 40-99% 60-97% 70-97% Water 0.01- 0.1-4% 0.2-2% 5% Flavors 0.05- 0.1-5% 0.1-2.5% 10% Propellant 2-10% 3-5% 3-4% B.
  • Prostaglandin E (vasodilator) Amount Preferred Amount Most-Preferred Amount prostaglandin 0.01- 0.1-5% 0.2-3% E 1 10% Ethanol 10-90% 20-75% 25-50% Propylene 1-90% 5-80% 10-75% glycol Water 0.01- 0.1-4% 0.2-2% 5% Flavors 0.05- 0.1-5% 0.1-2.5% 10% Propellant 2-10% 3-5% 3-4% C.
  • Promethazine antioxidant, sleep inducer, and CNS active amine
  • Amount Preferred Amount Most-Preferred Amount promethazine 1-25% 3-15% 5-12% Ethanol 10-90% 20-75% 25-50% Propylene 1-90% 5-80% 10-75% glycol Water 0.01- 0.1-4% 0.2-2% 5% Flavors 0.05- 0.1-5% 0.1-2.5% 10% Propellant 2-10% 3-5% 3-4% D.
  • Meclizine Amount Preferred Amount Most-Preferred Amount meclizine 1-25% 3-15% 5-12% Ethanol 1-15% 2-10% 3-6 Propylene 20-98% 5-90% 10-85% glycol Water 0.01- 0.1-4% 0.2-2% 5% Flavors 0.05- 0.1-5% 0.1-2.5% 10% Propellant 2-10% 3-5% 3-4%

Abstract

Buccal aerosol sprays or capsules using polar and non-polar solvent have now been developed which provide biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprise formulation I: aqueous polar solvent, active compound, and optional flavoring agent; formulation II: aqueous polar solvent, active compound, optionally flavoring agent, and propellant; formulation III: non-polar solvent, active compound, and optional flavoring agent; and formulation IV: non-polar solvent, active compound, optional flavoring agent, and propellant.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This application is a continuation-in-part of application Ser. No. 09/537,118, filed Mar. 29, 2000 which is a continuation-in-part of the U.S. national phase designation of PCT/US97/17899 filed Oct. 1, 1997, the disclosures of which are incorporated by reference herein in their entirety.[0001]
    • BACKGROUND OF THE INVENTION
  • It is known that certain biologically active compounds are better absorbed through the oral mucosa than through other routes of administration, such as through the stomach or intestine. However, formulations suitable for such administration by these latter routes present their own problems. For example, the biologically active compound must be compatible with the other components of the composition such as propellants, solvents, etc. Many such formulations have been proposed. For example, U.S. Pat. No. 4,689,233, Dvorsky et al., describes a soft gelatin capsule for the administration of the anti-coronary drug nifedipine dissolved in a mixture of polyether alcohols. U.S. Pat. No. 4,755,389, Jones et al., describes a hard gelatin chewable capsule containing nifedipine. A chewable gelatin capsule containing a solution or dispersion of a drug is described in U.S. Pat. No. 4,935,243, Borkan et al. U.S. Pat. No. 4,919,919, Aouda et al, and U.S. Pat. No. 5,370,862, Klokkers-Bethke, describe a nitroglycerin spray for administration to the oral mucosa comprising nitroglycerin, ethanol, and other components. An orally administered pump spray is described by Cholcha in U.S. Pat. No. 5,186,925. Aerosol compositions containing a hydrocarbon propellant and a drug for administration to a mucosal surface are described in U.K. 2,082,457, Su, U.S. Pat. No. 3,155,574, Silson et al., U.S. Pat. No. 5,011,678, Wang et al., and by Parnell in U.S. Pat. No. 5,128,132. It should be noted that these references discuss bioavailability of solutions by inhalation rather than through the membranes to which they are administered. [0002]
    • SUMMARY OF THE INVENTION
  • A buccal aerosol spray or soft bite gelatin capsule using a polar or non-polar solvent has now been developed which provides biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. [0003]
  • The buccal aerosol spray compositions of the present invention, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable non-polar solvent comprise in weight % of total composition: pharmaceutically acceptable propellant 5-80%, nonpolar solvent 19-85%, active compound 0.05-50%, suitably additionally comprising, by weight of total composition a flavoring agent 0.01-10%. Preferably the composition comprises: propellant 10-70%, non-polar solvent 25-89.9%, active compound 0.01-40%, flavoring agent 1-8%; most suitably propellant 20-70%, non-polar solvent 25-74.75%, active compound 0.25-35%, flavoring agent 2-7.5%. [0004]
  • The buccal polar aerosol spray compositions of the present invention, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent are also administrable in aerosol form driven by a propellant. In this case, the composition comprises in weight % of total composition: aqueous polar solvent 10-97%, active compound 0.1-25%, suitably additionally comprising, by weight of total composition a flavoring agent 0.05-10% and propellant: 2-10%. Preferably the composition comprises: polar solvent 20-97%, active compound 0.1-15%, flavoring agent 0.1-5% and propellant 2-5%; most suitably polar solvent 25-97%, active compound 0.2-25%, flavoring agent 0.1-2.5% and propellant 2-4%. [0005]
  • The buccal pump spray composition of the present invention, i.e., the propellant free composition, for transmucosal administration of a pharmacologically active compound wherein said active compound is soluble in a pharmacologically acceptable non-polar solvent comprises in weight % of total composition: non-polar solvent 30-99.69%, active compound 0.005-55%, and suitably additionally, flavoring agent 0.1-10%. [0006]
  • The buccal polar pump spray compositions of the present invention, i.e., the propellant free composition, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent comprises in weight % of total composition: aqueous polar solvent 30-99.69%, active compound 0.001-60%, suitably additionally comprising, by weight of total composition a flavoring agent 0.1-10%. Preferably the composition comprises: polar solvent 37-98.58%, active compound 0.005-55%, flavoring agent 0.5-8%; most suitably polar solvent 60.9-97.06%, active compound 0.01-40%, flavoring agent 0.75-7.5%. [0007]
  • The soft bite gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable non-polar solvent, having charged thereto a fill composition comprise in weight % of total composition: non-polar solvent 4-99.99%, emulsifier 0-20%, active compound 0.01-80%, provided that said fill composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 0.01-10%. Preferably, the soft bite gelatin capsule comprises: non-polar solvent 21.5-99.975%, emulsifier 0-15%, active compound 0.025-70%, flavoring agent 1-8%; most suitably: nonpolar solvent 28.5-97.9%, emulsifier 0-10%, active compound 0.1-65.0%, flavoring agent 2-6%. [0008]
  • The soft bite polar gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable polar solvent, having charged thereto a composition comprising in weight % of total composition: polar solvent 25-99.89%, emulsifier 0-20%, active compound 0.01-65%, provided that said composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 01-10%. Preferably, the soft bite gelatin capsule comprises: polar solvent 37-99.95%, emulsifier 0-15%, active compound 0.025-55%, flavoring agent 1-8%; most suitably: polar solvent 44-96.925%, emulsifier 0-10%, active compound 0.075-50%, flavoring agent 2-6%. [0009]
  • It is an object of the invention to coat the mucosal membranes either with extremely fine droplets of spray containing the active compounds or a solution or paste thereof from bite capsules. [0010]
  • It is also an object of the invention to administer to the oral mucosa of a mammalian in need of same, preferably man, by spray or bite capsule, a predetermined amount of a biologically active compound by this method or from a soft gelatin capsule. [0011]
  • A further object is a sealed aerosol spray container containing a composition of the non polar or polar aerosol spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition. [0012]
  • As the propellant evaporates after activation of the aerosol valve, a mist of fine droplets is formed which contains solvent and active compound. [0013]
  • The propellant is a non-Freon material, preferably a C[0014] 3-8 hydrocarbon of a linear or branched configuration. The propellant should be substantially non-aqueous. The propellant produces a pressure in the aerosol container such that under expected normal usage it will produce sufficient pressure to expel the solvent from the container when the valve is activated but not excessive pressure such as to damage the container or valve seals.
  • The non-polar solvent is a non-polar hydrocarbon, preferably a C[0015] 7-18 hydrocarbon of a linear or branched configuration, fatty acid esters, and triglycerides, such as miglyol. The solvent must dissolve the active compound and be miscible with the propellant, i.e., solvent and propellant must form a single phase at a temperature of 0-40° C. a pressure range of between 1-3 atm.
  • The polar and non-polar aerosol spray compositions of the invention are intended to be administered from a sealed, pressurized container. Unlike a pump spray, which allows the entry of air into the container after every activation, the aerosol container of the invention is sealed at the time of manufacture. The contents of the container are released by activation of a metered valve, which does not allow entry of atmospheric gasses with each activation. Such containers are commercially available. [0016]
  • A further object is a pump spray container containing a composition of the pump spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition. [0017]
  • A further object is a soft gelatin bite capsule containing a composition of as set forth above. The formulation may be in the form of a viscous solution or paste containing the active compounds. Although solutions are preferred, paste fills may also be used where the active compound is not soluble or only partially soluble in the solvent of choice. Where water is used to form part of the paste composition, it should not exceed 10% thereof. (All percentages herein are by weight unless otherwise indicated.) [0018]
  • The polar or non-polar solvent is chosen such that it is compatible with the gelatin shell and the active compound. The solvent preferably dissolves the active compound. However, other components wherein the active compound is not soluble or only slightly soluble may be used and will form a paste fill. [0019]
  • Soft gelatin capsules are well known in the art. See, for example, U.S. Pat. No. 4,935,243, Borkan et al., for its teaching of such capsules. The capsules of the present invention are intended to be bitten into to release the low viscosity solution or paste therein, which will then coat the buccal mucosa with the active compounds. Typical capsules, which are swallowed whole or bitten and then swallowed, deliver the active compounds to the stomach, which results in significant lag time before maximum blood levels can be achieved or subject the compound to a large first pass effect. Because of the enhanced absorption of the compounds through the oral mucosa and no chance of a first pass effect, use of the bite capsules of the invention will eliminate much of the lag time, resulting in hastened onset of biological effect. The shell of a soft gelatin capsule of the invention may comprise, for example: gelatin: 50-75%, glycerin 20-30%, colorants 0.5-1.5%, water 5-10%, and sorbitol 2-10%. [0020]
  • The active compound may include, biologically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostaglandins and neutraceuticals. [0021]
  • The active compounds may also include antihistamines, alkaloids, hormones, benzodiazepines and narcotic analgesics. While not limited thereto, these active compounds are particularly suitable for non-polar pump spray formulation and application. [0022]
  • The active compounds may also include p-FOX (fatty acid oxidation) inhibitors, acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, or a mixture thereof.[0023]
    • BRIEF DESCRIPTION OF THE DRAWING
  • FIG. 1. is a schematic diagram showing routes of absorption and processing of pharmacologically active substances in a mammalian system.[0024]
    • DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • The preferred active compounds of the present invention are in an ionized, salt form or as the free base of the pharmaceutically acceptable salts thereof (provided, for the aerosol or pump spray compositions, they are soluble in the spray solvent). These compounds are soluble in the non-polar solvents of the invention at useful concentrations or can be prepared as pastes at useful concentrations. These concentrations may be less than the standard accepted dose for these compounds since there is enhanced absorption of the compounds through the oral mucosa. This aspect of the invention is especially important when there is a large (40-99.99%) first pass effect. [0025]
  • As propellants for the non polar sprays, propane, N-butane, iso-butane, N-pentane, iso-pentane, and neo-pentane, and mixtures thereof may be used. N-butane and iso-butane, as single gases, are the preferred propellants. It is permissible for the propellant to have a water content of no more than 0.2%, typically 0.1-0.2%. All percentages herein are by weight unless otherwise indicated. It is also preferable that the propellant be synthetically produced to minimize the presence of contaminants which are harmful to the active compounds. These contaminants include oxidizing agents, reducing agents, Lewis acids or bases, and water. The concentration of each of these should be less than 0.1%, except that water may be as high as 0.2%. [0026]
  • Suitable non-polar solvents for the capsules and the non-polar sprays include (C[0027] 2-C24) fatty acid (C2-C6) esters, C7-C18 hydrocarbon, C2-C6 alkanoyl esters, and the triglycerides of the corresponding acids. When the capsule fill is a paste, other liquid components may be used instead of the above low molecular weight solvents. These include soya oil, corn oil, other vegetable oils.
  • As solvents for the polar capsules or sprays there may be used low molecular weight polyethyleneglycols (PEG) of 400-1000 Mw (preferably 400-600), low molecular weight (C[0028] 2-C8) mono and polyols and alcohols of C7-C18 linear or branch chain hydrocarbons, glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.
  • It is expected that some glycerin and water used to make the gelatin shell will migrate from the shell to the fill during the curing of the shell. Likewise, there may be some migration of components from the fill to the shell during curing and even throughout the shelf-life of the capsule. [0029]
  • Therefore, the values given herein are for the compositions as prepared, it being within the scope of the invention that minor variations will occur. [0030]
  • The preferred flavoring agents are synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners (sugars, aspartame, saccharin, etc.), and combinations thereof. [0031]
  • The active substances include the active compounds selected from the group consisting of cyclosporine, sermorelin, octreotide acetate, calcitonin-salmon, insulin lispro, sumatriptan succinate, clozepine, cyclobenzaprine, dexfenfluramine hydrochloride, glyburide, zidovudine, erythromycin, ciprofloxacin, ondansetron hydrochloride, dimenhydrinate, cimetidine hydrochloride, famotidine, phenytoin sodium, phenytoin, carboprost thromethamine, carboprost, diphenhydramine hydrochloride, isoproterenol hydrochloride, terbutaline sulfate, terbutaline, theophylline, albuterol sulfate and neutraceuticals, that is to say nutrients with pharmacological action such as but not limited to carnitine, valerian, echinacea, and the like. [0032]
  • In another embodiment, the active compound is a p-FOX (fatty acid oxidation) inhibitor, acetylcholinesterase inhibitor, nerve impulse inhibitor, anti-cholinergic, anti-convulsant, anti-psychotic, anxiolytic agent, dopamine metabolism inhibitor, agent to treat post stroke sequelae, neuroprotectant, agent to treat Alzheimer's disease, neurotransmitter, neurotransmitter agonist, sedative, agent for treating attention deficit disorder, agent for treating narcolepsy, central adregenic antagonist, anti-depression agent, agent for treating Parkinson's disease, benzodiazepine antagonist, stimulant, neurotransmitter antagonist, tranquilizer, or a mixture thereof. [0033]
  • In one embodiment the active compound is a p-FOX inhibitor. A suitable p-FOX inhibitor for use in the buccal sprays of the invention includes, but is not limited to, ranolazine. [0034]
  • In one embodiment the active compound is an acetylcholinesterase inhibitor. Suitable acetylcholinesterase inhibitors for use in the buccal sprays of the invention include, but are not limited to, galantamine, neostigmine, physostigmine, and edrophonium. [0035]
  • In one embodiment the active compound is a nerve impulse inhibitor. Suitable nerve impulse inhibitors for use in the buccal sprays of the invention include, but are not limited to, levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, and rocuronium. [0036]
  • In one embodiment the active compound is an anti-cholinergic. Suitable anti-cholinergics for use in the buccal sprays of the invention include, but are not limited to, amantadine, ipratropium, oxitropium, and dicycloverine. [0037]
  • In one embodiment the active compound is an anti-convulsant. Suitable anti-convulsants for use in the buccal sprays of the invention include, but are not limited to, acetazolamide, carbamazepine, clonazepam, diazepam, divalproex (valproic acid), ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, and zonisamide. [0038]
  • In one embodiment the active compound is an anti-psychotic. Suitable anti-psychotics for use in the buccal sprays of the invention include, but are not limited to, amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, and ziprasidone, [0039]
  • In one embodiment the active compound is an anxiolytic agent. Suitable anxiolytic agents for use in the buccal sprays of the invention include, but are not limited to, amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, and zopiclone. [0040]
  • In one embodiment the active compound is a dopamine metabolism inhibitor. Suitable dopamine metabolism inhibitors for use in the buccal sprays of the invention include, but are not limited to, entacapone, lazebemide, selegiline, and tolcapone. [0041]
  • In one embodiment the active compound is an agent to treat post stroke sequelae. Suitable agents to treat post stroke sequelae for use in the buccal sprays of the invention include, but are not limited to, glatiramer, interferon beta 1A, interferon beta 1B, estradiol, and progesterone. [0042]
  • In one embodiment the active compound is a neuroprotectant. Suitable neuroprotectants for use in the buccal sprays of the invention include, but are not limited to, donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, and xaliproden. [0043]
  • In one embodiment the active compound is an agent to treat Alzheimer's disease. Suitable agents to treat Alzheimer's disease for use in the buccal sprays of the invention include, but are not limited to, carbidopa, levodopa, tacrine, donezepil, rivastigmine, and galantamine. [0044]
  • In one embodiment the active compound is a neurotransmitter. Suitable neurotransmitters for use in the buccal sprays of the invention include, but are not limited to, acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, and nitric oxide. [0045]
  • In one embodiment the active compound is a neurotransmitter agonist. Suitable neurotransmitter agonists for use in the buccal sprays of the invention include, but are not limited to, almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, and zolmitriptan. [0046]
  • In one embodiment the active compound is a sedative. Suitable sedatives for use in the buccal sprays of the invention include, but are not limited to, dexmedetomidine, eszopiclone, indiplon, zolpidem, and zaleplon. [0047]
  • In one embodiment the active compound is an agent for treating attention deficit disorder. Suitable agents for treating attention deficit disorder for use in the buccal sprays of the invention include, but are not limited to, amphetamine, dextroamphetamine, methylphenidate, and pemoline. [0048]
  • In one embodiment the active compound is an agent for treating narcolepsy. Suitable agents for treating narcolepsy for use in the buccal sprays of the invention include, but are not limited to, modafinil and mazindol. [0049]
  • In one embodiment the active compound is a central adregenic antagonists. A suitable central adregenic antagonists for use in the buccal sprays of the invention includes, but is not limited to, mesoridazine. [0050]
  • In one embodiment the active compound is an anti-depression agent. Suitable anti-depression agents for use in the buccal sprays of the invention include, but are not limited to, amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, and venlafaxine. [0051]
  • In one embodiment the active compound is an agent for treating Parkinson's disease. Suitable agents for treating Parkinson's disease for use in the buccal sprays of the invention include, but are not limited to, amantadine, bromocriptine, carvidopa, levodopa, pergolide, and selegiline. [0052]
  • In one embodiment the active compound is a benzodiazepine antagonist. A suitable benzodiazepine antagonist for use in the buccal sprays of the invention includes, but is not limited to, flumazenil. [0053]
  • In one embodiment the active compound is a neurotransmitter antagonist. A suitable neurotransmitter antagonist for use in the buccal sprays of the invention includes, but is not limited, to deramciclane. [0054]
  • In one embodiment the active compound is a stimulant. Suitable stimulants for use in the buccal sprays of the invention include, but are not limited to, amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, and pemoline. [0055]
  • In one embodiment the active compound is a tranquilizer. A suitable tranquilizer for use in the buccal sprays of the invention includes, but is not limited to, mesoridazine. [0056]
  • The formulations of the present invention comprise an active compound or a pharmaceutically acceptable salt thereof. The term “pharmaceutically acceptable salts” refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases including organic and inorganic acids or bases. [0057]
  • When an active compound of the present invention is acidic, salts may be prepared from pharmaceutically acceptable non-toxic bases. Salts derived from all stable forms of inorganic bases include aluminum, ammonium, calcium, copper, iron, lithium, magnesium, manganese, potassium, sodium, zinc, etc. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion-exchange resins such as arginine, betaine, caffeine, choline, N,N dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethyl-aminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, isopropylamine, lysine, methyl-glucosamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purine, theobromine, triethylamine, trimethylamine, tripropylamine, etc. [0058]
  • When an active compound of the present invention is basic, salts may be prepared from pharmaceutically acceptable non-toxic acids. Such acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethane-sulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, etc. Particularly preferred are citric, hydrobromic, maleic, phosphoric, sulfuric, and tartaric acids. [0059]
  • In the discussion of methods of treatment herein, reference to the active compounds is meant to also include the pharmaceutically acceptable salts thereof. While certain formulations are set forth herein, the actual amounts to be administered to the mammal or man in need of same are to be determined by the treating physician. [0060]
  • The invention is further defined by reference to the following examples, which are intended to be illustrative and not limiting. [0061]
  • The following are examples of certain classes. All values unless otherwise specified are in weight percent. [0062]
    • EXAMPLES Example 1
  • Biologically Active Peptides Including Peptide Hormones [0063]
    A. Cyclosporine lingual spray
    Amounts preferred amount most preferred amount
    cyclosporine  5-50 10-35 15-25
    water  5-20 7.5-50  9.5-12 
    ethanol  5-60 7.5-50  10-20
    polyethylene 20-60 30-45 35-40
    glycol
    flavors 0.1-5   1-4 2-3
    B. Cyclosporine Non-Polar lingual spray
    Amounts preferred amount most preferred amount
    cyclosporine  1-50  3-40  5-30
    Migylol 20 25 30-40
    Poly- 20 25 30-40
    oxyethylated
    castor oil
    Butane 25-80 30-70 33-50
    flavors 0.1-5   1-4 2-3
    C. Cyclosporine non-polar bite caosule
    Amounts preferred amount most preferred amount
    cyclosporine  1-35  5-25 10-20
    olive oil 25-60 35-55 30-45
    poly- 25-60 35-55 30-45
    oxyethylated
    oleic glycerides
    flavors 0.1-5   1-4 2-3
    D. Cyclosporine bite capsule
    Amounts preferred amount most preferred amount
    cyclosporine  5-50 10-35 15-25
    polyethylene 20-60 30-45 35-40
    glycol
    glycerin  5-30 7.5-25  10-20
    propylene  5-30 7.5-25  10-20
    glycol
    flavors 0.1-10  1-8 3-6
    E. Sermorelin (as the acetate) lingual spray
    Amounts preferred amount most preferred
    sermorelin (as .01-5   .1-3   .2-1.0
    the acetate)
    mannitol  1-25  5-20 10-15
    monobasic 0.1-5    1-31  .5-2.5
    sodium
    phosphate,
    dibasic sodium 0.01-5   .05-3   0.1-0.5
    phosphate
    water
    ethanol  5-30 7.5-25  9.5-15 
    polyethylene 20-60 30-45 35-40
    glycol
    propylene  5-25 10-20 12-17
    glycol
    flavors 0.1-5   1-4 2-3
    F. Octreotide acetate (Sandostatin) lingual spray
    Amounts preferred amount most preferred amount
    octreotide 0.001-0.5  0.005-0.250 0.01-0.10
    acetate
    acetic acid  1-10 2-8 4-6
    sodium acetate  1-10 2-8 4-6
    sodium  3-30  .5-25 15-20
    chloride
    flavors 0.1-5   0.5-.4  2-3
    ethanol  5-30 7.5-20  9.5-15 
    water 15-95 35-90 65-85
    flavors 0.1-5   1-4 2-3
    G. Calcitonin-salmon lingual spray
    Amounts preferred amount most preferred amount
    calcitonin- 0.001-5    0.005-2     01-1.5
    salmon
    ethanol  2-15  3-10   7-9.5
    water 30-95 50-90 60-80
    polyethylene  2-15  3-10   7-9.5
    glycol
    sodium 2.5-20   5-15   10-12.5
    chloride
    flavors 0.1-5   1-4 2-3
    H. Insulin lispro, lingual spray
    Amounts preferred amount most preferred amount
    insulin 20-60  4-55  5-50
    glycerin 0.1-10  0.25-5   0.1-1.5
    dibasic sodium  1-15 2.5-10  4-8
    phosphate
    m-cresol,  1-25  5-25  7.5-12.5
    zinc oxide 0.01-0.25   .05-0.15 0.075-0.10 
    m-cresol 0.1-1   0.2-0.8 0.4-0.6
    phenol trace trace amounts trace amounts
    amounts
    ethanol  5-20 7.5-15   9-12
    water 30-90 40-80 50-75
    propylene  5-20 7.5-15   9-12
    glycol
    flavors 0.1-5   0.5-3   0.75-2  
    adjust pH to 7.0-7.8 with HCI or NaOH
    • Example 2
  • CNS active amines and their salts: including but not limited to tricyclic amines, GABA analogues, thiazides, phenothiazine derivatives, serotonin antagonists and serotonin reuptake inhibitors [0064]
    A. Sumatriptan succinate lingual spray
    Amounts preferred amount most preferred amount
    sumatriptan 0.5-30  1-20 10-15
    succinate
    ethanol  5-60 7.5-50  10-20
    propylene  5-30 7.5-20  10-15
    glycol
    polyethylene  0-60 30-45 35-40
    glycol
    water  5-30 7.5-20  10-15
    flavors 0.1-5   1-4 2-3
    B. Sumatriptan succinate bite capsule
    Amounts preferred amount most preferred amount
    sumatriptan 0.01-5   0.05-3.5  0.075-1.75 
    succinate
    polyethylene 25-70 30-60 35-50
    glycol
    glycerin 25-70 30-60 35-50
    flavors 0.1-10  1-8 3-6
    C. Clozepine lingual spray
    Amounts preferred amount most preferred amount
    clozepine 0.5-30   1-20 10-15
    ethanol  5-60 7.5-50  10-20
    propylene  5-30 7.5-20  10-15
    glycol
    polyethylene  0-60 30-45 35-40
    glycol
    water  5-30 7.5-20  10-15
    flavors 0.1-5   1-4 2-3
    D. Clozepine non-polar linaual spray with propellant
    Amounts preferred amount most preferred amount
    clozepine 0.5-30   1-20 10-15
    Migylol 20-85 25-70 30-40
    Butanol  5-80 30-75 60-70
    flavors 0.1-5   1-4 2-3
    E. Clozepine non-polar lingual spray without propellant
    Amounts preferred amount most preferred amount
    clozepine 0.5-30   1-20 10-15
    Migylol   70-99.5 80-99 85-90
    flavors 0.1-5   1-4 2-3
    F. Cyclobenzaprine non-polar lingual spray
    Amounts preferred amount most preferred amount
    cyclobenzaprine 0.5-30   1-20 10-15
    (base)
    Migylol 20-85 25-70 30-40
    Iso-butane 15-80 30-75 60-70
    flavors 0.1-5   1-4 2-3
    G. Dexfenflurarnine hydrochloride lingual spray
    Amounts preferred amount most preferred amount
    dexfenfluramine  5-30 7.5-20  10-15
    Hcl
    ethanol  5-60 7.5-50  10-20
    propylene  5-30 7.5-20  10-15
    glycol
    polyethylene  0-60 30-45 35-40
    glycol
    water  5-30 7.5-20  10-15
    flavors 0.1-5   1-4 2-3
    • Example 3 Sulfonylureas
  • [0065]
    A. Glyburide lingual spray
    Amounts preferred amount most preferred amount
    glyburide 0.25-25   0.5-20  0.75-15  
    ethanol  5-60 −7.5-50   10-20
    propylene  5-30 7.5-20  10-15
    glycol
    polyethylene  0-60 30-45 35-40
    glycol
    water 2.5-30   5-20  6-15
    flavors 0.1-5   1-4 2-3
    B. Glyburide non-polar bite capsule
    Amounts preferred amount most preferred amount
    glyburide 0.01-10   0.025-7.5  0.1-4  
    olive oil 30-60 35-55 30-50
    polyoxyethylated
    oleic
    glycerides 30-60 35-55 30-50
    flavors 0.1-5   1-4 2-3
    • Example 4 Antibiotics Anti-fungals and Anti-virals
  • [0066]
    A. Zidovudine [formerly called azidothymidine (AZT) (Retrovir)] non-
    polar lingual spray
    Amounts preferred amount most preferred amount
    zidovudine 10-50 15-40 25-35
    Soya oil 20-85 25-70 30-40
    Butane 15-80 30-75 60-70
    flavors 0.1-5   1-4 2-3
    B. Erythromycin bite capsule bite capsule
    Amounts preferred amount most preferred amount
    erythromycin 25-65 30-50 35-45
    polyoxyethylene  5-70 30-60 45-55
    glycol
    glycerin  5-20 7.5-15    10-12.5
    flavors  1-10 2-8 3-6
    C. Ciprofloxacin hydrochloride bite capsule
    Amounts preferred amount most preferred amount
    ciprofloxacin 25-65 35-55 40-50
    hydrochloride
    glycerin  5-20 7.5-15    10-12.5
    polyethylene 120-75  30-65 40-60
    glycol
    flavors  1-10 2-8 3-6
    D. zidovudine [formerly called azidothymidine (AZT) (Retrovir]
    lingual spray
    Amounts preferred amount most preferred amount
    zidovudine 10-50 15-40 25-35
    water 30-80 40-75 45-70
    ethanol  5-20 7.5-15   9.5-12.5
    polyethylene  5-20 7.5-15   9.5-12.5
    glycol
    flavors 0.1-5   1-4 2-3
    • Example 5
  • Anti-Emetics [0067]
    A. Ondansetron hydrochloride lingual spray
    Amounts preferred amount most preferred amount
    ondansetron  1-25  2-20 2.5-15 
    hydrochloride
    citric acid  1-10 2-8 2.5-5  
    monohydrate
    sodium citrate 0.5-5   1-4 1.25-2.5 
    dihydrate
    water  1-90  5-85 10-75
    ethanol  5-30 7.5-20  9.5-15 
    propylene  5-30 7.5-20  9.5-15 
    glycol
    polyethylene  5-30 7.5-20  9.5-15 
    glycol
    flavors  1-10 3-8   5-7.5
    B. Dimenhydrinate bite capsule
    Amounts preferred amount most preferred amount
    dimenhydrinate 0.5-30   2-25  3-15
    glycerin  5-20 7.5-15    10-12.5
    polyethylene 45-95 50-90 55-85
    glycol
    flavors  1-10 2-8 3-6
    C. Dimenhydrinate polar lingual spray
    Amounts preferred amount most preferred amount
    dimenhydrinate  3-50  4-40  5-35
    water  5-90 10-80 15-75
    ethanol  1-80  3-50  5-10
    polyethylene  1-80  3-50  5-15
    glycol
    sorbitol 0.1-5   0.2-40  0.4-1.0
    aspartame 0.01-0.5  0.02-0.4  0.04-0.1 
    flavors 0.1-5   1-4 2-3
    • Example 6
  • Histamine H-2 Receptor Antagonists [0068]
    A. Cimetidine hydrochloride bite capsule
    Amounts preferred amount most preferred amount
    cimetidine HCl 10-60 15-55 25-50
    glycerin  5-20 7.5-15    10-12.5
    polyethylene 20-90 25-85 30-75
    glycol
    flavors  1-10 2-8 3-6
    B. Famotidine lingual spray
    Amounts preferred amount most preferred amount
    famotidine  1-35  5-30  7-20
    water 2.5-25   3-20  5-10
    L-aspartic 0.1-20   1-15  5-10
    acid
    polyethylene 20-97 30-95 50-85
    glycol
    flavors 0.1-10    1-7.5 2-5
    C. Famotidine non-polar lingual spray
    Amounts preferred amount most preferred amount
    famotidine  1-35  5-30  7-20
    Soya oil 10-50 15-40 15-20
    Butanel  5-80 30-75 45-70
    poly- 10-50 15-40 15-20
    oxyethylated
    oleic glycerides
    flavors 0.1-5   1-4 2-3
    • Example 7 Barbiturates
  • [0069]
    A. Phenytoin sodium lingual spray
    Amounts preferred amount most preferred amount
    phenytoin 10-60 15-55 20-40
    sodium
    water 2.5-25   3-20  5-10
    ethanol  5-30 7.5-20  9.5-15 
    propylene  5-30 7.5-20  9.5-15 
    glycol
    polyethylene  5-30 7.5-20  9.5-15 
    glycol
    flavors  1-10 3-8   5-7.5
    B. Phenytoin non-polar lingual spray
    Amounts preferred amount most preferred amount
    phenytoin  5-45 10-40 15-35
    migylol 10-50 15-40 15-20
    Butane 15-80 30-75 60-70
    polyoxyethylated 10-50 15-40 15-20
    oleic glycerides
    flavors 0.1-10  1-8   5-7.5
    • Example 8 Prostaglandins
  • [0070]
    A. Carboprost thromethamine lingual spray
    Amounts preferred amount most preferred amount
    carboprost 0.05-5   0.1-3   0.25-2.5 
    thromethamine
    water 50-95 60-80 65-75
    ethanol  5-20 7.5-15   9.5-12.5
    polyethylene  5-20 7.5-15   9.5-12.5
    glycol
    sodium chloride  1-20  3-15 4-8
    flavors 0.1-5   1-4 2-3
    pH is adjusted with sodium hydroxide and/or hydrochloric acid
    B. Carboprost non-polar lingual spray
    Amounts preferred amount most preferred amount
    carboprost 0.05-5   0.1-3   0.25-2.5 
    migylol 25-50 30-45 35-40
    Butane  5-60 10-50 20-35
    polyoxyethylated 25-50 30-45 35-40
    oleic glycerides
    flavors 0.1-10  1-8   5-7.5
    • Example 9 Neutraceuticals
  • [0071]
    A. Carnitine as bite capsule (contents are a pastel
    Amounts preferred amount most preferred amount
    camitine  6-80 30-70 45-65
    fumarate
    soya oil 7.5-50  10-40 12.5-35
    soya lecithin 0.001- 0.005-0.5  .01-0.1
    1.0 
    Soya fats 7.5-50  10-40 12.5-35  
    flavors  1-10 2-8 3-6
    B. Valerian as lingual spray
    Amounts preferred amount most preferred amount
    valerian extract 0.1-10  0.2-7   0.25-5  
    water 50-95 60-80 65-75
    ethanol  5-20 7.5-15   9.5-12.5
    polyethylene  5-20 7.5-15   9.5-12.5
    glycol
    flavors  1-10 2-8 3-6
    C. Echinacea as bite capsule
    Amounts preferred amount most preferred amount
    echinacea 30-85 40-75 45-55
    extract
    soya oil 7.5-50  10-40 12.5-35  
    soya lecithin 0.001- 0.005-0.5  .01-0.1
    1.0 
    Soya fats 7.5-50  10-40 12.5-35  
    flavors  1-10 2-8 3-6
    D. Mixtures of ingredients
    Amounts preferred amount most preferred amount
    magnesium oxide 15-40 20-35 25-30
    chromium 0.01-1.0  0.02-0.5  .025-0.75
    picolinate
    folic acid .025-3.0  0.05-2.0  0.25-0.5 
    vitamin B-12 0.01-1.0  0.02-0.5  .025-0.75
    vitamin E 15-40 20-35 25-30
    Soya oil 10-40 12.5-35 12 15-20
    soya lecithin 0.1-5   0.2-4   0.5-1.5
    soya fat 10-40 15-35 17.5-20  
    • Example 10 Sleep Inducers (Also CNS Active Amine)
  • [0072]
    A. Diphenhydramine hydrochloride lingual spray
    Amounts preferred amount most preferred amount
    diphenhydramine   3-50.  4-40  5-35
    HCl water  5-90 10-80 50-75
    ethanol  1-80  3-50  5-10
    polyethylene  1-80  3-50  5-15
    glycol
    Sorbitol 0.1-5   0.2-4   0.4-1.0
    aspartame 0.01-0.5  0.02-0.4  0.04-0.1 
    flavors 0.1-5   1-4 2-3
    • Example 11 Anti-asthmatics-bronchodilators
  • [0073]
    A. Isoproterenol Hydrochloride as polar lingual spray
    Amounts preferred amount most preferred amount
    isoproterenol 0.1-10  0.2-7.5 0.5-6  
    Hydrochloride
    water  5-90 10-80 50-75
    ethanol  1-80  3-50  5-10
    polyethylene  1-80  3-50  5-15
    glycol
    Sorbitol 0.1-5   0.2-4   0.4-1.0
    aspartame 0.01-0.5  0.02-0.4  0.04-0.1 
    flavors 0.1-5   1-4 2-3
    B. Terbutaline sulfate as polar lingual spray
    Amounts preferred amount most preferred amount
    terbutaline 0.1-10  0.2-7.5 0.5-6  
    sulfate
    water  5-90 10-80 50-75
    ethanol  1-10 2-8 2.5-5  
    Sorbitol 0.1-5   0.2-4   0.4-1.0
    aspartame 0.01-0.5  0.02-0.4  0.04-0.1 
    flavors 0.1-5   1-4 2-3
    C. Terbutaline as non-polar lingual spray
    Amounts preferred amount most preferred amount
    terbutaline 0.1-10  0.2-7.5 0.5-6  
    migylol 25-50 30-45 35-40
    isobutane  5-60 10-50 20-35
    polyoxyethylated 25-50 30-45 35-40
    oleic glycerides
    flavors 0.1-10  1-8   5-7.5
    D. Theophylline polar bite capsule
    Amounts preferred amount most preferred amount
    theophylline  5-50 10-40 15-30
    polyethylene 20-60 25-50 30-40
    glycol
    glycerin 25-50 35-45 30-40
    propylene 25-50 35-45 30-40
    glycol
    flavors 0.1-5   1-4 2-3
    E. Albuterol sulfate as polar lingual spray
    Amounts preferred amount most preferred amount
    albuterol 0.1-10  0.2-7.5 0.5-6  
    sulfate
    water  5-90 10-80 50-75
    ethanol  1-10 2-8 2.5-5  
    Sorbitol 0.1-5   0.2-4   0.4-1.0
    aspartame 0.01-0.5  0.02-0.4  0.04-0.1 
    flavors 0.1-5   1-4 2-3
    • Example 12
  • Polar Solvent Formulations Using a Propellant: [0074]
    A. Sulfonylurea
    Amount Preferred Amount Most-Preferred Amount
    glyburide 0.1-25%  0.5-15%  0.6-10% 
    Ethanol 40-99% 60-97% 70-97%
    Water 0.01- 0.1-4%   0.2-2%  
     5%
    Flavors 0.05- 0.1-5%   0.1-2.5%
    10%
    Propellant  2-10% 3-5% 3-4%
    B. Prostaglandin E (vasodilator)
    Amount Preferred Amount Most-Preferred Amount
    prostaglandin 0.01- 0.1-5%   0.2-3%  
    E1 10%
    Ethanol 10-90% 20-75% 25-50%
    Propylene  1-90%  5-80% 10-75%
    glycol
    Water 0.01- 0.1-4%   0.2-2%  
     5%
    Flavors 0.05- 0.1-5%   0.1-2.5%
    10%
    Propellant  2-10% 3-5% 3-4%
    C. Promethazine (antiemetic, sleep inducer, and CNS active amine)
    Amount Preferred Amount Most-Preferred Amount
    promethazine  1-25%  3-15%  5-12%
    Ethanol 10-90% 20-75% 25-50%
    Propylene  1-90%  5-80% 10-75%
    glycol
    Water 0.01- 0.1-4%   0.2-2%  
     5%
    Flavors 0.05- 0.1-5%   0.1-2.5%
    10%
    Propellant  2-10% 3-5% 3-4%
    D. Meclizine
    Amount Preferred Amount Most-Preferred Amount
    meclizine  1-25%  3-15%  5-12%
    Ethanol  1-15%  2-10% 3-6 
    Propylene 20-98%  5-90% 10-85%
    glycol
    Water 0.01- 0.1-4%   0.2-2%  
     5%
    Flavors 0.05- 0.1-5%   0.1-2.5%
    10%
    Propellant  2-10% 3-5% 3-4%

Claims (123)

What is claimed is:
1. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount of between 0.001 and 60 percent by weight of the total composition selected from the group consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof, and
a polar solvent in an amount between 30 and 99 percent by weight of the total composition.
2. The composition of claim 1, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.
3. The composition of claim 2, wherein the polar solvent is present in an amount between 37 and 98 percent by weight of the total composition, the active compound is present in an amount between 0.005 and 55 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.5 and 8 percent by weight of the total composition.
4. The composition of claim 3, wherein the polar solvent is present in an amount between 60 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.01 and 40 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.75 and 7.5 percent by weight of the total composition.
5. The composition of claim 1, wherein the polar solvent is selected from the group consisting of polyethylene glycols having a molecular weight between 400 and 1000, C2 to C8 mono- and poly-alcohols, and C7 to C18 alcohols of linear or branched configuration.
6. The composition of claim 1, wherein the polar solvent comprises aqueous polyethylene glycol.
7. The composition of claim 1, wherein the polar solvent comprises aqueous ethanol.
8. The composition of claim 1, wherein the active compound is an acetylcholinesterase inhibitors selected from the group consisting of galantamine, neostigmine, physostigmine, and edrophonium, and mixtures thereof.
9. The composition of claim 1, wherein the active compound is a nerve impulse inhibitor selected from the group consisting of levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, rocuronium, and mixtures thereof.
10. The composition of claim 1, wherein the active compound is an anti-cholinergic selected from the group consisting of amantadine, ipratropium, oxitropium, dicycloverine, and mixtures thereof.
11. The composition of claim 1, wherein the active compound is an anti-convulsant selected from the group consisting of acetazolamide, carbamazepine, clonazepam, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide, and mixtures thereof.
12. The composition of claim 1, wherein the active compound is an anti-psychotic selected from the group consisting of amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, ziprasidone, and mixtures thereof.
13. The composition of claim 1, wherein the active compound is an anxiolytic agent selected from the group consisting of amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, zopiclone, and mixtures thereof.
14. The composition of claim 1, wherein the active compound is a dopamine metabolism inhibitor selected from the group consisting of entacapone, lazebemide, selegiline, tolcapone, and mixtures thereof.
15. The composition of claim 1, wherein the active compound is an agent to treat post stroke sequelae selected from the group consisting of glatiramer, interferon beta 1A, interferon beta 1B, estradiol, progesterone, and mixtures thereof.
16. The composition of claim 1, wherein the active compound is a neuroprotectant selected from the group consisting of donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, xaliproden, and mixtures thereof.
17. The composition of claim 1, wherein the active compound is an agent to treat Alzheimer's disease selected from the group consisting of carbidopa, levodopa, tacrine, donezepil, rivastigmine, galantamine, and mixtures thereof.
18. The composition of claim 1, wherein the active compound is a neurotransmitter selected from the group consisting of acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, nitric oxide, and mixtures thereof.
19. The composition of claim 1, wherein the active compound is a neurotransmitter agonist selected from the group consisting of almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan, and mixtures thereof.
20. The composition of claim 1, wherein the active compound is a sedative selected from the group consisting of dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon, and mixtures thereof.
21. The composition of claim 1, wherein the active compound is an agent for treating attention deficit disorder selected from the group consisting of amphetamine, dextroamphetamine, methylphenidate, pemoline, and mixtures thereof.
22. The composition of claim 1, wherein the active compound is an agent for treating narcolepsy selected from the group consisting of modafinil, mazindol, and mixtures thereof.
23. The composition of claim 1, wherein the active compound is an anti-depression agent selected from the group consisting of amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, venlafaxine, and mixtures thereof.
24. The composition of claim 1, wherein the active compound is an agent for treating Parkinson's disease selected from the group consisting of amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline, and mixtures thereof.
25. The composition of claim 1, wherein the active compound is the benzodiazepine antagonist flumazenil.
26. The composition of claim 1, wherein the active compound is the neurotransmitter antagonist deramciclane.
27. The composition of claim 1, wherein the active compound is a stimulant selected from the group consisting of amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline, and mixtures thereof.
28. The composition of claim 1, wherein the active compound is the tranquilizer mesoridazine.
29. The composition of claim 2, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
30. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 1.
31. The method of claim 30, wherein the amount of the spray is predetermined.
32. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount of between 0.1 and 25 percent by weight of the total composition selected from the group consisting of consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof;
a polar solvent in an amount between 10 and 97 percent by weight of the total composition; and
a propellant in an amount between 2 and 10 percent by weight of the total composition, wherein said propellant is a C3 to C8 hydrocarbon of linear or branched configuration.
33. The composition of claim 32, further comprising a flavoring agent in an amount between 0.05 and 10 percent by weight of the total composition.
34. The composition of claim 33, wherein the polar solvent is present in an amount between 20 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.1 and 15 percent by weight of the total composition, the propellant is present in an amount between 2 and 5 percent by weight of the composition, and the flavoring agent is present in an amount between 0.1 and 5 percent by weight of the total composition.
35. The composition of claim 34, wherein the polar solvent is present in an amount between 25 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.2 and 25 percent by weight of the total composition, the propellant is present in an amount between 2 and 4 percent by weight of the composition, and flavoring agent is present in an amount between 0.1 and 2.5 percent by weight of the total composition.
36. The composition of claim 32, wherein the polar solvent is selected from the group consisting of polyethyleneglycols having a molecular weight between 400 and 1000, C2 to C8 mono- and poly-alcohols, and C7 to C18 alcohols of linear or branched configuration.
37. The composition of claim 36, wherein the polar solvent comprises aqueous polyethylene glycol.
38. The composition of claim 36, wherein the polar solvent comprises aqueous ethanol.
39. The composition of claim 32, wherein the active compound is an acetylcholinesterase inhibitors selected from the group consisting of galantamine, neostigmine, physostigmine, and edrophonium, and mixtures thereof.
40. The composition of claim 32, wherein the active compound is a nerve impulse inhibitor selected from the group consisting of levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, rocuronium, and mixtures thereof.
41. The composition of claim 32, wherein the active compound is an anti-cholinergic selected from the group consisting of amantadine, ipratropium, oxitropium, dicycloverine, and mixtures thereof.
42. The composition of claim 32, wherein the active compound is an anti-convulsant selected from the group consisting of acetazolamide, carbamazepine, clonazepam, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide, and mixtures thereof.
43. The composition of claim 32, wherein the active compound is an anti-psychotic selected from the group consisting of amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, ziprasidone, and mixtures thereof.
44. The composition of claim 32, wherein the active compound is an anxiolytic agent selected from the group consisting of amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, zopiclone, and mixtures thereof.
45. The composition of claim 32, wherein the active compound is a dopamine metabolism inhibitor selected from the group consisting of entacapone, lazebemide, selegiline, tolcapone, and mixtures thereof.
46. The composition of claim 32, wherein the active compound is an agent to treat post stroke sequelae selected from the group consisting of glatiramer, interferon beta 1A, interferon beta 1B, estradiol, progesterone, and mixtures thereof.
47. The composition of claim 32, wherein the active compound is a neuroprotectant selected from the group consisting of donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, xaliproden, and mixtures thereof.
48. The composition of claim 32, wherein the active compound is an agent to treat Alzheimer's disease selected from the group consisting of carbidopa, levodopa, tacrine, donezepil, rivastigmine, galantamine, and mixtures thereof.
49. The composition of claim 32, wherein the active compound is a neurotransmitter selected from the group consisting of acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, nitric oxide, and mixtures thereof.
50. The composition of claim 32, wherein the active compound is a neurotransmitter agonist selected from the group consisting of almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan, and mixtures thereof.
51. The composition of claim 32, wherein the active compound is a sedative selected from the group consisting of dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon, and mixtures thereof.
52. The composition of claim 32, wherein the active compound is an agent for treating attention deficit disorder selected from the group consisting of amphetamine, dextroamphetamine, methylphenidate, pemoline, and mixtures thereof.
53. The composition of claim 32, wherein the active compound is an agent for treating narcolepsy selected from the group consisting of modafinil, mazindol, and mixtures thereof.
54. The composition of claim 32, wherein the active compound is an anti-depression agent selected from the group consisting of amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, venlafaxine, and mixtures thereof.
55. The composition of claim 32, wherein the active compound is an agent for treating Parkinson's disease selected from the group consisting of amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline, and mixtures thereof.
56. The composition of claim 32, wherein the active compound is the benzodiazepine antagonist flumazenil.
57. The composition of claim 32, wherein the active compound is the neurotransmitter antagonist deramciclane.
58. The composition of claim 32, wherein the active compound is a stimulant selected from the group consisting of amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline, and mixtures thereof.
59. The composition of claim 32, wherein the active compound is the tranquilizer mesoridazine.
60. The composition of claim 32, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
61. The composition of claim 32, wherein the propellant is selected from the group consisting of propane, N-butane, iso-butane, N-pentane, iso-pentane, neo-pentane, and mixtures thereof.
62. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 32.
63. The method of claim 62, wherein the amount of the spray is predetermined.
64. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount between 0.005 and 55 percent by weight of the total composition selected from the group consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof; and
a non-polar solvent in an amount between 30 and 99 percent by weight of the total composition.
65. The composition of claim 64, further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition.
66. The composition of claim 64, wherein the active compound is an acetylcholinesterase inhibitors selected from the group consisting of galantamine, neostigmine, physostigmine, and edrophonium, and mixtures thereof.
67. The composition of claim 64, wherein the active compound is a nerve impulse inhibitor selected from the group consisting of levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, rocuronium, and mixtures thereof.
68. The composition of claim 64, wherein the active compound is an anti-cholinergic selected from the group consisting of amantadine, ipratropium, oxitropium, dicycloverine, and mixtures thereof.
69. The composition of claim 64, wherein the active compound is an anti-convulsant selected from the group consisting of acetazolamide, carbamazepine, clonazepam, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide, and mixtures thereof.
70. The composition of claim 64, wherein the active compound is an anti-psychotic selected from the group consisting of amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, ziprasidone, and mixtures thereof.
71. The composition of claim 64, wherein the active compound is an anxiolytic agent selected from the group consisting of amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, zopiclone, and mixtures thereof.
72. The composition of claim 64, wherein the active compound is a dopamine metabolism inhibitor selected from the group consisting of entacapone, lazebemide, selegiline, tolcapone, and mixtures thereof.
73. The composition of claim 64, wherein the active compound is an agent to treat post stroke sequelae selected from the group consisting of glatiramer, interferon beta 1A, interferon beta 1B, estradiol, progesterone, and mixtures thereof.
74. The composition of claim 64, wherein the active compound is a neuroprotectant selected from the group consisting of donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, xaliproden, and mixtures thereof.
75. The composition of claim 64, wherein the active compound is an agent to treat Alzheimer's disease selected from the group consisting of carbidopa, levodopa, tacrine, donezepil, rivastigmine, galantamine, and mixtures thereof.
76. The composition of claim 64, wherein the active compound is a neurotransmitter selected from the group consisting of acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, nitric oxide, and mixtures thereof.
77. The composition of claim 64, wherein the active compound is a neurotransmitter agonist selected from the group consisting of almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan, and mixtures thereof.
78. The composition of claim 64, wherein the active compound is a sedative selected from the group consisting of dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon, and mixtures thereof.
79. The composition of claim 64, wherein the active compound is an agent for treating attention deficit disorder selected from the group consisting of amphetamine, dextroamphetamine, methylphenidate, pemoline, and mixtures thereof.
80. The composition of claim 64, wherein the active compound is an agent for treating narcolepsy selected from the group consisting of modafinil, mazindol, and mixtures thereof.
81. The composition of claim 64, wherein the active compound is an anti-depression agent selected from the group consisting of amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, venlafaxine, and mixtures thereof.
82. The composition of claim 64, wherein the active compound is an agent for treating Parkinson's disease selected from the group consisting of amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline, and mixtures thereof.
83. The composition of claim 64, wherein the active compound is the benzodiazepine antagonist flumazenil.
84. The composition of claim 64, wherein the active compound is the neurotransmitter antagonist deramciclane.
85. The composition of claim 64, wherein the active compound is a stimulant selected from the group consisting of amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline, and mixtures thereof.
86. The composition of claim 64, wherein the active compound is the tranquilizer mesoridazine.
87. The composition of claim 65, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
88. The composition of claim 64, wherein the solvent is selected from the group consisting of (C2-C24) fatty acid (C2-C6) esters, C7-C18 hydrocarbons of linear or branched configuration, C2-C6 alkanoyl esters, and triglycerides of C2-C6 carboxylic acids.
89. The composition of claim 88, wherein the solvent is miglyol.
90. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 64.
91. The method of claim 90, wherein the amount of the spray is predetermined.
92. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount between 0.05 and 50 percent by weight of the total composition selected from the group consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof; and
a non-polar solvent in an amount between 19 and 85 percent by weight of the total composition; and
a propellant in an amount between 5 and 80 percent by weight of the total composition, wherein said propellant is a C3 to C8 hydrocarbon of linear or brancehed configuration.
93. The composition of claim 92, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.
94. The composition of claim 93, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
95. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount between 0.01 and 40 percent by weight of the total composition selected from the group consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof; and
a non-polar solvent in an amount between 25 and 89 percent by weight of the total composition;
a propellant in an amount between 10 and 70 percent by weight of the total composition, wherein said propellant is a C3 to C8 hydrocarbon of linear or brancehed configuration; and
A flavoring agent is present in an amount between 1 and 8 percent by weight of the total composition.
96. The composition of claim 95, wherein the propellant is present in an amount between 20 and 70 percent by weight of the total composition, the non-polar solvent is present in an amount between 25 and 75 percent by weight of the total composition, the active compound is present in an amount from between 0.25 and 35 percent by weight of the total composition, and the flavoring agent is present in an amount between 2 and 7.5 percent by weight of the total composition.
97. The composition of claim 92, wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pantane, iso-pentane, neo-pentane, and mixtures thereof.
98. The composition of claim 97, wherein the propellant is n-butane or iso-butane and has a water content of not more than 0.2 percent and a concentration of oxidizing agents, reducing agents, Lewis acids, and Lewis bases of less than 0.1 percent.
99. The composition of claim 92, wherein the solvent is selected from the group consisting of (C2-C24) fatty acid (C2-C6) esters, C7-C18 hydrocarbons of linear or branched configuration, C2-C6 alkanoyl esters, and triglycerides of C2-C6 carboxylic acids.
100. The composition of claim 99, wherein the solvent is miglyol.
101. The composition of claim 92, wherein the active compound is an acetylcholinesterase inhibitors selected from the group consisting of galantamine, neostigmine, physostigmine, and edrophonium, and mixtures thereof.
102. The composition of claim 92, wherein the active compound is a nerve impulse inhibitor selected from the group consisting of levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, rocuronium, and mixtures thereof.
103. The composition of claim 92, wherein the active compound is an anti-cholinergic selected from the group consisting of amantadine, ipratropium, oxitropium, dicycloverine, and mixtures thereof.
104. The composition of claim 92, wherein the active compound is an anti-convulsant selected from the group consisting of acetazolamide, carbamazepine, clonazepam, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide, and mixtures thereof.
105. The composition of claim 92, wherein the active compound is an anti-psychotic selected from the group consisting of amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, ziprasidone, and mixtures thereof.
106. The composition of claim 92, wherein the active compound is an anxiolytic agent selected from the group consisting of amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, zopiclone, and mixtures thereof.
107. The composition of claim 92, wherein the active compound is a dopamine metabolism inhibitor selected from the group consisting of entacapone, lazebemide, selegiline, tolcapone, and mixtures thereof.
108. The composition of claim 92, wherein the active compound is an agent to treat post stroke sequelae selected from the group consisting of glatiramer, interferon beta 1A, interferon beta 1B, estradiol, progesterone, and mixtures thereof.
109. The composition of claim 92, wherein the active compound is a neuroprotectant selected from the group consisting of donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, xaliproden, and mixtures thereof.
110. The composition of claim 92, wherein the active compound is an agent to treat Alzheimer's disease selected from the group consisting of carbidopa, levodopa, tacrine, donezepil, rivastigmine, galantamine, and mixtures thereof.
111. The composition of claim 92, wherein the active compound is a neurotransmitter selected from the group consisting of acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, nitric oxide, and mixtures thereof.
112. The composition of claim 92, wherein the active compound is a neurotransmitter agonist selected from the group consisting of almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan, and mixtures thereof.
113. The composition of claim 92, wherein the active compound is a sedative selected from the group consisting of dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon, and mixtures thereof.
114. The composition of claim 92, wherein the active compound is an agent for treating attention deficit disorder selected from the group consisting of amphetamine, dextroamphetamine, methylphenidate, pemoline, and mixtures thereof.
115. The composition of claim 92, wherein the active compound is an agent for treating narcolepsy selected from the group consisting of modafinil, mazindol, and mixtures thereof.
116. The composition of claim 92, wherein the active compound is an anti-depression agent selected from the group consisting of amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, venlafaxine, and mixtures thereof.
117. The composition of claim 92, wherein the active compound is an agent for treating Parkinson's disease selected from the group consisting of amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline, and mixtures thereof.
118. The composition of claim 92, wherein the active compound is the benzodiazepine antagonist flumazenil.
119. The composition of claim 92, wherein the active compound is the neurotransmitter antagonist deramciclane.
120. The composition of claim 92, wherein the active compound is a stimulant selected from the group consisting of amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline, and mixtures thereof.
121. The composition of claim 92, wherein the active compound is the tranquilizer mesoridazine.
122. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 92.
123. The method of claim 122, wherein the amount of the spray is predetermined.
US10/230,060 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system Abandoned US20030077227A1 (en)

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US10/230,060 US20030077227A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
AU2003298564A AU2003298564A1 (en) 2002-08-29 2003-08-27 Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
PCT/US2003/026847 WO2004035021A2 (en) 2002-08-29 2003-08-27 Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
CA002497262A CA2497262A1 (en) 2002-08-29 2003-08-27 Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
EP10181730A EP2283815A1 (en) 2002-08-29 2003-08-27 Propellant-free non polar buccal spray of a sedative
EP10181701A EP2283814B1 (en) 2002-08-29 2003-08-27 Polar buccal spray of zolpidem
EP10181746A EP2277506A1 (en) 2002-08-29 2003-08-27 Non-polar buccal spray of a sedative
JP2004545251A JP2006505569A (en) 2002-08-29 2003-08-27 Oral polar and nonpolar sprays or capsules containing therapeutics for diseases of the central nervous system
EP03796314A EP1539106A2 (en) 2002-08-29 2003-08-27 Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
EP10181677A EP2283813B1 (en) 2002-08-29 2003-08-27 Propellant-free polar buccal spray of zolpidem
US10/671,720 US20040141923A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing alprazolam
US10/671,715 US7632517B2 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing zolpidem
US10/671,709 US20050163719A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing diazepam
US10/726,585 US6977070B2 (en) 1997-10-01 2003-12-04 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US10/834,815 US20050002867A1 (en) 1997-10-01 2004-04-27 Buccal, polar and non-polar sprays containing propofol
US11/384,444 US20060159624A1 (en) 1997-10-01 2006-03-21 Buccal, polar and non-polar spray containing zolpidem
US11/391,297 US20060171896A1 (en) 1997-10-01 2006-03-29 Buccal, polar and non-polar spray containing alprazolam
US11/442,137 US20060222597A1 (en) 1997-10-01 2006-05-30 Buccal, polar and non-polar sprays containing propofol
US11/443,254 US20060216241A1 (en) 1997-10-01 2006-05-31 Buccal, polar and non-polar spray containing diazepam
US11/443,253 US20060216240A1 (en) 1997-10-01 2006-05-31 Buccal, polar and non-polar spray containing zolpidem
US12/350,915 US20090131514A1 (en) 1997-10-01 2009-01-08 Buccal, polar and non-polar sprays containing propofol
US12/351,275 US20090186099A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US12/394,903 US20090162300A1 (en) 1997-10-01 2009-02-27 Buccal, polar and non-polar spray containing alprazolam
US12/576,457 US8236285B2 (en) 1997-10-01 2009-10-09 Buccal, polar and non-polar spray containing zolpidem
US13/208,429 US20110293536A1 (en) 1997-10-01 2011-08-12 Buccal, polar and non-polar spray containing zolipidem
US16/130,860 US20190083471A1 (en) 2002-08-29 2018-09-13 Buccal, polar and non-polar spray containing zolipidem
US16/665,622 US20200061034A1 (en) 2002-08-29 2019-10-28 Buccal, polar and non-polar spray containing zolipidem

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US53711800A 2000-03-29 2000-03-29
US10/230,060 US20030077227A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system

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US10/671,720 Continuation-In-Part US20040141923A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing alprazolam
US10/671,709 Continuation-In-Part US20050163719A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing diazepam
US10/671,715 Continuation-In-Part US7632517B2 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing zolpidem
US10/726,585 Division US6977070B2 (en) 1997-10-01 2003-12-04 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US10/834,815 Continuation-In-Part US20050002867A1 (en) 1997-10-01 2004-04-27 Buccal, polar and non-polar sprays containing propofol
US11/391,297 Continuation-In-Part US20060171896A1 (en) 1997-10-01 2006-03-29 Buccal, polar and non-polar spray containing alprazolam
US12/351,275 Continuation US20090186099A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system

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US10/726,585 Expired - Fee Related US6977070B2 (en) 1997-10-01 2003-12-04 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US12/351,275 Abandoned US20090186099A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system

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Cited By (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030077229A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20030077228A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20030082107A1 (en) * 1997-10-01 2003-05-01 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20030095925A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030185761A1 (en) * 1997-10-01 2003-10-02 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20030190286A1 (en) * 1997-10-01 2003-10-09 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20040062716A1 (en) * 1997-10-01 2004-04-01 Novadel Pharma Inc. Buccal, polar and non-polar spray of capsule
WO2004035021A2 (en) * 2002-08-29 2004-04-29 Novadel Pharma Inc. Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US20050002867A1 (en) * 1997-10-01 2005-01-06 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
WO2005030167A2 (en) * 2003-09-29 2005-04-07 Novadel Pharma Inc. Buccal, polar and non-polar spray containing alprazolam
WO2005032517A1 (en) * 2003-09-29 2005-04-14 Novadel Pharma Inc. Buccal, polar and non-polar spray containing diazepam
WO2005032519A1 (en) * 2003-09-29 2005-04-14 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
WO2005037193A2 (en) * 2003-10-03 2005-04-28 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor administered under hypothermic conditions for the treatment of ischemic mediated central nervous system disorders or injury
WO2005046615A2 (en) * 2003-11-12 2005-05-26 Pharmacia & Upjohn Company Llc Compositions for treatment of central nervous system mediated disorders
US6919378B2 (en) * 2000-10-11 2005-07-19 Cephalon, Inc. Pharmaceutical solutions of modafinil compounds
US20050171088A1 (en) * 2004-01-30 2005-08-04 Astrazeneca Ab Treatment of psychoses with dibenzothiazepine antipsychotic
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US20050226925A1 (en) * 2004-02-17 2005-10-13 Transoral Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US6977257B2 (en) * 2001-04-25 2005-12-20 Bristol-Myers Squibb Company Aripiprazole oral solution
US20050281752A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20050287075A1 (en) * 1997-10-01 2005-12-29 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20060062812A1 (en) * 2003-03-11 2006-03-23 Calvin Ross Novel compositions
US20060198790A1 (en) * 1997-10-01 2006-09-07 Dugger Harry A Iii Buccal, polar and non-polar spray containing ondansetron
WO2006125774A1 (en) * 2005-05-25 2006-11-30 Janssen Pharmaceutica N.V. Pediatric formulation of topiramate
US20060276501A1 (en) * 2005-05-25 2006-12-07 Transoral Pharmaceuticals, Inc. Solid compositions for treating middle-of-the-night insomnia
US20070225322A1 (en) * 2005-05-25 2007-09-27 Transoral Pharmaceuticals, Inc. Compositions and methods for treating middle-of-the night insomnia
US20070248548A1 (en) * 2006-04-19 2007-10-25 Blondino Frank E Stable hydroalcoholic oral spray formulations and methods
US20070287740A1 (en) * 2005-05-25 2007-12-13 Transcept Pharmaceuticals, Inc. Compositions and methods of treating middle-of-the night insomnia
DE102006032427A1 (en) * 2006-07-13 2008-01-17 Neuraxpharm Arzneimittel Gmbh U. Co. Kg Use of composition comprising e.g. clozapine, quetiapine, olanzapine, benzyl- and/or phenylethyl alcohol, ethanol, ethereal oil, sweetener, and polyethylene glycol, for preparing an orally administering solution to treat schizophrenia
DE102006032426A1 (en) * 2006-07-13 2008-01-17 Neuraxpharm Arzneimittel Gmbh U. Co. Kg Use of a composition comprising e.g. clozapine and quetiapine; benzyl- and/or phenylethyl alcohol; propylene glycol; ethereal oil; and polyethylene glycol, for preparing an orally administering solution to treat schizophrenia
US20080021016A1 (en) * 2004-03-12 2008-01-24 Levay Gyoergy Combined Pharmaceutical Composition for the Inhibition of the Decline of Cognitive Functions
US20080081067A1 (en) * 2006-10-03 2008-04-03 Gupta Manishkumar Sustained release pharmaceutical compositions of venlafaxine and process for preparation thereof
US20080171089A1 (en) * 2006-12-22 2008-07-17 Blondino Frank E Stable anti-nausea oral spray formulations and methods
US20080213363A1 (en) * 2003-01-23 2008-09-04 Singh Nikhilesh N Methods and compositions for delivering 5-HT3 antagonists across the oral mucosa
US20080280947A1 (en) * 2007-05-10 2008-11-13 Blondino Frank E Anti-insomnia compositions and methods
US20090107836A1 (en) * 2007-10-30 2009-04-30 Novellus Systems, Inc. Closed Contact Electroplating Cup Assembly
US20090162300A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing alprazolam
US20090162298A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing sumatriptan
US20100192945A1 (en) * 2008-12-23 2010-08-05 Robert Owen Cook Inhalation devices and related methods for administration of sedative hypnotic compounds
US20100196286A1 (en) * 2008-12-01 2010-08-05 Armer Thomas A Inhalation delivery methods and devices
US20100317694A1 (en) * 2004-10-19 2010-12-16 Krka, Tovarna Zdravil, D.D. , Novo Mesto Solid pharmaceutical composition comprising donepezil hydrochloride
US20110021588A1 (en) * 2009-05-15 2011-01-27 Recro Pharma, Inc. Sublingual dexmeditomidine compositions and methods of use thereof
US20110086845A1 (en) * 2007-07-10 2011-04-14 The Board Of Trustees Of The University Of Illinois Compositions and Methods for Treating Neurodegenerating Diseases
US20110124656A1 (en) * 2009-11-20 2011-05-26 Tonix Pharmaceuticals, Inc. Methods and Compositions for Treating Symptoms Associated with Post-Traumatic Stress Disorder using Cyclobenzaprine
EP2526925A1 (en) 2011-05-23 2012-11-28 Deva Holding Anonim Sirketi A dose adjustable oral pump spray or aerosol spray containing memantine
US8470862B2 (en) 1999-10-29 2013-06-25 Recro Pharma, Inc. Treatment or prevention of hypotension and shock
WO2013188847A1 (en) 2012-06-15 2013-12-19 Tonix Pharmaceuticals, Inc. Compositions and methods for transmucosal absorption
EP2767163A1 (en) 2005-02-17 2014-08-20 Abbott Laboratories Transmucosal administration of drug compositions for treating and preventing disorders in animals
US9474728B2 (en) 2010-06-24 2016-10-25 Tonix Pharma Holdings Limited Methods and compositions for treating fatigue associated with disordered sleep using very low dose cyclobenzaprine
US9585893B2 (en) 2011-02-23 2017-03-07 Coeruleus Ltd. Flumazenil complexes, compositions comprising same and uses thereof
US9636408B2 (en) 2013-03-15 2017-05-02 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US9795559B2 (en) 2011-12-11 2017-10-24 Recro Pharma, Inc. Intranasal dexmedetomidine compositions and methods of use thereof
CN109010323A (en) * 2018-08-27 2018-12-18 北京普瑞博思投资有限公司 Molten film of rivastigmine-hydrogentartrate mouth and preparation method thereof
CN109106697A (en) * 2012-11-09 2019-01-01 丝维塔斯治疗公司 The high dose levodopa capsule used for lung
US10357465B2 (en) 2014-09-18 2019-07-23 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride
CN112390767A (en) * 2021-01-19 2021-02-23 嘉实（湖南）医药科技有限公司 Preparation method of eperisone hydrochloride impurity F
US11433046B2 (en) * 2019-12-10 2022-09-06 Tulex Pharmaceuticals Inc. Compositions and methods for treating epilepsy, seizures and other conditions
US11826321B2 (en) 2017-12-11 2023-11-28 Tonix Pharma Holdings Limited Cyclobenzaprine treatment for agitation, psychosis and cognitive decline in dementia and neurodegenerative conditions

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030095926A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20050059656A1 (en) * 2003-04-07 2005-03-17 Cornell Research Foundation, Inc. Compositions and methods for protecting against mitochondria component-mediated pathology
NZ527142A (en) * 2003-07-23 2006-03-31 Douglas Pharmaceuticals Ltd A stable suspension formulation
WO2005065673A1 (en) * 2003-12-31 2005-07-21 Actavis Group Hf Atomoxetine formulations
JP2007537274A (en) * 2004-05-10 2007-12-20 ナステック ファーマスーティカル カンパニー インク． Compositions and methods for enhancing mucosal delivery of parathyroid hormone
US7888346B2 (en) * 2004-09-24 2011-02-15 Universtiy of Maryland, Baltimore Method of treating organophosphorous poisoning
US9132135B2 (en) * 2004-09-24 2015-09-15 University Of Maryland, Baltimore Method of treating organophosphorous poisoning
CN101132781A (en) * 2004-12-09 2008-02-27 茵西斯医疗公司 Room-temperature stable dronabinol formulations
EP1904066B1 (en) * 2005-07-06 2018-05-23 Sunovion Pharmaceuticals Inc. COMBINATIONS OF ESZOPICLONE AND TRANS 4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-N-METHYL-1-NAPTHALENAMINE OR TRANS 4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-1-NAPTHALENAMINE, for treating MENOPAUSE, perimenopause AND COGNITIVE DISORDERS
ES2535233T3 (en) 2006-01-25 2015-05-06 Insys Therapeutics, Inc. Spraying sublingual fentanyl
ES2360423T3 (en) * 2006-04-26 2011-06-03 Supernus Pharmaceuticals, Inc. OXCARBAZEPIN CONTROLLED RELEASE PREPARATIONS THAT HAVE SIGMOIDAL RELEASE PROFILE.
EP2068831A4 (en) * 2006-07-28 2010-07-21 Novadel Pharma Inc Anti-migraine oral spray formulations and methods
BRPI0715328A2 (en) * 2006-08-04 2013-07-09 Insys Therapeutics Inc formulation and unit dose or multiple dose device for sublingual administration of a drug
WO2008019431A1 (en) * 2006-08-14 2008-02-21 Brc Operations Pty Limited Method and compositions for simultaneously regulating memory and mood
FR2906140B1 (en) * 2006-09-22 2008-12-05 Philippe Perovitch GALENIC FORM FOR TRANSMUCOSUS ADMINISTRATION OF ACTIVE INGREDIENTS
US20080275030A1 (en) 2007-01-19 2008-11-06 Sveinbjorn Gizurarson Methods and Compositions for the Delivery of a Therapeutic Agent
US8486973B2 (en) 2007-08-02 2013-07-16 Insys Therapeutics, Inc. Sublingual fentanyl spray
EP2184983A1 (en) * 2007-08-06 2010-05-19 Insys Therapeutics Inc. Oral cannabinoid liquid formulations and methods of treatment
CA2622696A1 (en) * 2007-11-05 2009-05-05 Diane Mcintosh Methods and compositions for retarding weight gain associated with use of atypical antipsychotic drugs
AU2009223153A1 (en) * 2008-03-12 2009-09-17 Emory University Use of GABAa receptor antagonists for the treatment of excessive sleepiness and disorders associated with excessive sleepiness
SG157299A1 (en) 2008-05-09 2009-12-29 Agency Science Tech & Res Diagnosis and treatment of kawasaki disease
BR112012012945A2 (en) 2009-11-25 2020-12-29 Arisgen Sa MUCOSAL RELEASE COMPOSITION, ITS PRODUCTION METHOD, PRE-FORMED PEPTIDE COMPLEX, KIT AND USE OF AN ACTIVE PEPTIDE AGENT
EP2327394A1 (en) * 2009-11-26 2011-06-01 Almirall, S.A. Liquid pharmaceutical composition
EP2526971A1 (en) 2011-05-25 2012-11-28 ArisGen SA Mucosal delivery of drugs
BR112015014957A2 (en) * 2012-12-21 2017-07-11 Map Pharmaceuticals Inc fluoroergoline derivatives and uses thereof
WO2015140790A1 (en) 2014-03-17 2015-09-24 Mapi Pharma Ltd. Sublingual delivery of glatiramer acetate
AU2016222550B2 (en) 2015-02-27 2020-07-16 Dechra Limited Stimulation of appetite, management of weight loss, and treatment of anorexia in dogs and cats
US11331271B2 (en) 2016-05-27 2022-05-17 The Johns Hopkins University Buccal, sublingual and intranasal delivery of fospropofol
GB2571696B (en) 2017-10-09 2020-05-27 Compass Pathways Ltd Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced
CA3081615A1 (en) * 2017-11-03 2019-05-09 Psychnostics, Llc Combination therapies for treating bipolar disorder and adhd, and methods for using the same
CN113993523A (en) 2019-04-17 2022-01-28 指南针探路者有限公司 Treatment of depression and other various disorders with siloxibin
US11071739B1 (en) 2020-09-29 2021-07-27 Genus Lifesciences Inc. Oral liquid compositions including chlorpromazine

Citations (78)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3155574A (en) * 1962-05-24 1964-11-03 Revlon Aerosol composition
US3304230A (en) * 1963-02-18 1967-02-14 Revlon Liquid aerosol propellant solutions of fatty acid salts of physiologically active amines
US3784684A (en) * 1971-08-24 1974-01-08 Bayer Ag Coronary dilator in a pharmaceutical dosage unit form
US4232002A (en) * 1977-12-01 1980-11-04 The Welsh National School Of Medicine Procedures and pharmaceutical products for use in the administration of antihistamines
US4495168A (en) * 1983-08-22 1985-01-22 Basf Wyandotte Corporation Aerosol gel
US4689233A (en) * 1986-01-06 1987-08-25 Siegfried Aktiengesellschaft Coronary therapeutic agent in the form of soft gelatin capsules
US4704406A (en) * 1985-06-24 1987-11-03 Klinge Pharma Gmbh Sprayable pharmaceutical composition for topical use
US4755389A (en) * 1985-09-11 1988-07-05 Lilly Industries Limited Chewable capsules
US4814161A (en) * 1985-01-16 1989-03-21 Riker Laboratories, Inc. Drug-containing chlorofluorocarbon aerosol propellent formulations
US4857312A (en) * 1985-12-18 1989-08-15 Bayer Aktiengesellschaft Dihydropyridine spray, process for its preparation and its pharmaceutical use
US4863720A (en) * 1986-03-10 1989-09-05 Walter Burghart Pharmaceutical preparation and methods for its production
US4863970A (en) * 1986-11-14 1989-09-05 Theratech, Inc. Penetration enhancement with binary system of oleic acid, oleins, and oleyl alcohol with lower alcohols
US4919919A (en) * 1987-09-30 1990-04-24 Nippon Kayaku Kabushiki Kaisha Nitroglycerin spray
US4935243A (en) * 1988-12-19 1990-06-19 Pharmacaps, Inc. Chewable, edible soft gelatin capsule
US5011678A (en) * 1989-02-01 1991-04-30 California Biotechnology Inc. Composition and method for administration of pharmaceutically active substances
US5047230A (en) * 1988-07-08 1991-09-10 Egis Gyogyszergyar Aerosol composition comprising nitroglycerin as active ingredient
US5128132A (en) * 1988-11-22 1992-07-07 Parnell Pharmaceuticals, Inc. Eriodictyon compositions and methods for treating internal mucous membranes
US5135753A (en) * 1991-03-12 1992-08-04 Pharmetrix Corporation Method and therapeutic system for smoking cessation
US5143731A (en) * 1990-08-07 1992-09-01 Mediventures Incorporated Body cavity drug delivery with thermo-irreversible polyoxyalkylene and ionic polysaccharide gels
US5166145A (en) * 1990-09-10 1992-11-24 Alza Corporation Antiemetic therapy
US5186925A (en) * 1990-03-10 1993-02-16 G. Pohl-Boskamp Gmbh & Co. Nitroglycerin pump spray
US5240932A (en) * 1990-03-30 1993-08-31 Yasunori Morimoto Percutaneously absorbable compositions of morphine or analogous analgesics of morphine
US5290540A (en) * 1991-05-01 1994-03-01 Henry M. Jackson Foundation For The Advancement Of Military Medicine Method for treating infectious respiratory diseases
US5364616A (en) * 1992-04-15 1994-11-15 The Procter & Gamble Company Use of H-2 antagonists for treatment of gingivitis
US5428006A (en) * 1990-05-10 1995-06-27 Bechgaard International Research And Development A/S Method of administering a biologically active substance
US5456677A (en) * 1994-08-22 1995-10-10 Spector; John E. Method for oral spray administration of caffeine
US5457100A (en) * 1991-12-02 1995-10-10 Daniel; David G. Method for treatment of recurrent paroxysmal neuropsychiatric
US5502076A (en) * 1994-03-08 1996-03-26 Hoffmann-La Roche Inc. Dispersing agents for use with hydrofluoroalkane propellants
US5593684A (en) * 1993-08-04 1997-01-14 Pharmacia Ab Method and therapeutic system for smoking cessation
US5602182A (en) * 1995-01-30 1997-02-11 American Home Products Corporation Taste masking pseudoephedrine HCL containing liquids
US5605674A (en) * 1988-12-06 1997-02-25 Riker Laboratories, Inc. Medicinal aerosol formulations
US5607915A (en) * 1992-09-29 1997-03-04 Inhale Therapeutic Systems Pulmonary delivery of active fragments of parathyroid hormone
US5635161A (en) * 1995-06-07 1997-06-03 Abbott Laboratories Aerosol drug formulations containing vegetable oils
US5645856A (en) * 1994-03-16 1997-07-08 R. P. Scherer Corporation Delivery systems for hydrophobic drugs
US5719197A (en) * 1988-03-04 1998-02-17 Noven Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
US5725841A (en) * 1993-03-17 1998-03-10 Minnesota Mining And Manufacturing Company Aerosol formulation containing an ester-, amide-, or mercaptoester-derived dispersing aid
US5766573A (en) * 1988-12-06 1998-06-16 Riker Laboratories, Inc. Medicinal aerosol formulations
US5795909A (en) * 1996-05-22 1998-08-18 Neuromedica, Inc. DHA-pharmaceutical agent conjugates of taxanes
US5824307A (en) * 1991-12-23 1998-10-20 Medimmune, Inc. Human-murine chimeric antibodies against respiratory syncytial virus
US5869082A (en) * 1996-04-12 1999-02-09 Flemington Pharmaceutical Corp. Buccal, non-polar spray for nitroglycerin
US5891465A (en) * 1996-05-14 1999-04-06 Biozone Laboratories, Inc. Delivery of biologically active material in a liposomal formulation for administration into the mouth
US5906811A (en) * 1997-06-27 1999-05-25 Thione International, Inc. Intra-oral antioxidant preparations
US5908611A (en) * 1995-05-05 1999-06-01 The Scripps Research Institute Treatment of viscous mucous-associated diseases
US5955098A (en) * 1996-04-12 1999-09-21 Flemington Pharmaceutical Corp. Buccal non polar spray or capsule
US5981591A (en) * 1992-12-04 1999-11-09 Mayor Pharmaceutical Laboratories, Inc. Sprayable analgesic composition and method of use
US6071539A (en) * 1996-09-20 2000-06-06 Ethypharm, Sa Effervescent granules and methods for their preparation
US6110486A (en) * 1996-04-12 2000-08-29 Flemington Pharmaceuticals Co. Buccal polar spray or capsule
US6143329A (en) * 1996-07-03 2000-11-07 Rorer Pharmaceutical Products Inc. Aqueous-based pharmaceutical composition
US6212227B1 (en) * 1997-12-02 2001-04-03 Conexant Systems, Inc. Constant envelope modulation for splitterless DSL transmission
US6258032B1 (en) * 1997-01-29 2001-07-10 William M. Hammesfahr Method of diagnosis and treatment and related compositions and apparatus
US6271240B1 (en) * 1996-05-06 2001-08-07 David Lew Simon Methods for improved regulation of endogenous dopamine in prolonged treatment of opioid addicted individuals
US6299900B1 (en) * 1996-02-19 2001-10-09 Monash University Dermal penetration enhancers and drug delivery systems involving same
US6375975B1 (en) * 1998-12-21 2002-04-23 Generex Pharmaceuticals Incorporated Pharmaceutical compositions for buccal and pulmonary application
US20020102218A1 (en) * 2000-12-01 2002-08-01 Cowan Siu Man L. Stable, aerosolizable suspensions of proteins in ethanol
US6458842B1 (en) * 1994-02-01 2002-10-01 Knoll Aktiengesellschaft Liquid pharmaceutical compositions comprising thyroid hormones
US6512002B2 (en) * 2000-01-12 2003-01-28 Pfizer Inc. Methods of treatment for premature ejaculation in a male
US20030039680A1 (en) * 1997-10-01 2003-02-27 Flemington Pharmaceutical Corporation Buccal, polar and non-polar spray or capsule
US20030077229A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20030077228A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20030082107A1 (en) * 1997-10-01 2003-05-01 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20030095925A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20030095926A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030185761A1 (en) * 1997-10-01 2003-10-02 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20030191180A1 (en) * 2000-03-09 2003-10-09 Calvin Ross Pharmaceutical compositions
US20030190286A1 (en) * 1997-10-01 2003-10-09 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20040120895A1 (en) * 1997-10-01 2004-06-24 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US20040136914A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing ondansetron
US20040136913A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing sumatriptan
US20040141923A1 (en) * 1997-10-01 2004-07-22 Dugger Harry A. Buccal, polar and non-polar spray containing alprazolam
US6816452B1 (en) * 1999-07-14 2004-11-09 Sumitomo Electric Industries, Ltd. Vehicle-to-roadside communication system, roadside communication station, and on-board mobile station
US20050002867A1 (en) * 1997-10-01 2005-01-06 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20050163719A1 (en) * 1997-10-01 2005-07-28 Dugger Harry A.Iii Buccal, polar and non-polar spray containing diazepam
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US20060159624A1 (en) * 1997-10-01 2006-07-20 Dugger Harry A Iii Buccal, polar and non-polar spray containing zolpidem
US20070045229A1 (en) * 2002-03-11 2007-03-01 Keenan Joseph F System and method for the manufacture of surgical blades
US7202233B2 (en) * 2000-03-28 2007-04-10 Farmarc Nederland Bv Alprazolam inclusion complexes and pharmaceutical compositions thereof

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA815698B (en) 1980-08-28 1983-04-27 Lilly Co Eli Intranasal formulation
DE3338978A1 (en) 1982-10-29 1984-05-03 Basf Ag, 6700 Ludwigshafen Verapamil and gallopamil and their physiologically tolerated salts for application onto the mucous membranes of the mouth, of the naso-pharyngeal space and of the rectum for absorption
DE3246081A1 (en) 1982-12-13 1984-06-14 G. Pohl-Boskamp GmbH & Co Chemisch-pharmazeutische Fabrik, 2214 Hohenlockstedt Nitroglycerin spray
IT1169873B (en) * 1983-10-21 1987-06-03 Prodotti Formenti Srl PHARMACEUTICAL COMPOSITION WITH SYSTEMIC ANTI-COLINESTERASIC, AGONISTIC-COLINERGIC AND ANTI-MUSCARINIC ACTIVITY
EP0213108A3 (en) 1985-06-26 1987-07-15 Kurt Dr. Burghart Pharmaceutical preparation containing an antihypotonic as the active agent
DE3738236A1 (en) 1987-11-11 1989-05-24 Euro Celtique Sa BIT CAPSULE
AU2252388A (en) 1988-05-02 1989-11-29 Zila Pharmaceuticals Compositions and in situ methods for forming films on body tissue
DE3907414A1 (en) 1989-03-08 1990-09-13 Hoechst Ag THE APPLICATION OF INHALED LOOP DIURETICS FOR THE TREATMENT OF ALLERGEN-INDUCED NASAL REACTIONS
IL94466A (en) 1989-05-25 1995-01-24 Erba Carlo Spa Pharmaceutical compositions containing n-phenylalkyl substituted alpha-amino carboxamide derivatives, some such novel compounds and their preparation
DE4000770A1 (en) 1990-01-12 1991-07-18 Reynolds Aluminium Deutschland CONNECTION OF THE JOINT BETWEEN BAR AND POST ON A CARRIER FOR ONE OR ON A FAÇADE WALL
US5370862A (en) 1990-06-13 1994-12-06 Schwarz Pharma Ag Pharmaceutical hydrophilic spray containing nitroglycerin for treating angina
DE4026072A1 (en) 1990-08-17 1992-02-20 Sanol Arznei Schwarz Gmbh NITROGLYCER-CONTAINING, HYDROPHILIC, WAESSRING PUMPSPRAY
DE4038203A1 (en) 1990-11-30 1992-06-04 Kali Chemie Pharma Gmbh Pharmaceutical spray-prepn. for admin. of nitrate(s) - esp. for treatment of cardiovascular, disorders, asthma, migraine and colic
EP0504112A3 (en) 1991-03-14 1993-04-21 Ciba-Geigy Ag Pharmaceutical aerosol formulations
DE4112303A1 (en) 1991-04-15 1992-10-22 Minnesota Mining & Mfg Nitroglycerin, propellant gas-free spray prepn. - stored in container in which the steel parts are made of V4A series steels to inhibit nitroglycerin decomposition
PT656207E (en) * 1991-06-10 2001-11-30 Schering Corp AEROSOLS FORMULATIONS WITHOUT CHLOROFLUOROCARBONETS
GB9118830D0 (en) * 1991-09-03 1991-10-16 Minnesota Mining & Mfg Medical aerosol formulations
DE4132176C2 (en) 1991-09-27 1997-03-13 Ig Spruehtechnik Gmbh Metered aerosols with isobutane as propellant
ATE144884T1 (en) 1992-02-20 1996-11-15 Wielligh Johannes Louw Kot Von PRODUCT TO SUPPORT TO QUIT SMOKING
WO1994013280A1 (en) 1992-12-04 1994-06-23 Mayor Pharmaceutical Laboratories, Inc. Sprayable analgesic composition and method of use
WO1995031182A1 (en) * 1994-05-13 1995-11-23 Aradigm Corporation Narcotic containing aerosol formulation
US5519059A (en) * 1994-08-17 1996-05-21 Sawaya; Assad S. Antifungal formulation
NZ280610A (en) 1994-12-29 1997-08-22 Mcneil Ppc Inc Soft gelatin-like pharmaceutical carrier: gelled polyethylene glycol and dispersed active agent
US6517860B1 (en) 1996-12-31 2003-02-11 Quadrant Holdings Cambridge, Ltd. Methods and compositions for improved bioavailability of bioactive agents for mucosal delivery
US6461591B1 (en) * 1997-02-05 2002-10-08 Jago Research Ag Medical aerosol formulations
US20090162300A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing alprazolam
US6037346A (en) * 1997-10-28 2000-03-14 Vivus, Inc. Local administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction
MXPA01004828A (en) 1998-11-12 2002-09-18 Frank G Pilkiewicz An inhalation system.
GB9908921D0 (en) 1999-04-19 1999-06-16 Britannia Pharmaceuticals Ltd Spray dispenser for opiod antagonists
WO2002094232A1 (en) * 2001-05-24 2002-11-28 Alexza Molecular Delivery Corporation Delivery of antidepressants through an inhalation route
US6685951B2 (en) * 2001-07-05 2004-02-03 R. T. Alamo Ventures I, Inc. Administration of dihydroergotamine as a sublingual spray or aerosol for the treatment of migraine

Patent Citations (99)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3155574A (en) * 1962-05-24 1964-11-03 Revlon Aerosol composition
US3304230A (en) * 1963-02-18 1967-02-14 Revlon Liquid aerosol propellant solutions of fatty acid salts of physiologically active amines
US3784684A (en) * 1971-08-24 1974-01-08 Bayer Ag Coronary dilator in a pharmaceutical dosage unit form
US4232002A (en) * 1977-12-01 1980-11-04 The Welsh National School Of Medicine Procedures and pharmaceutical products for use in the administration of antihistamines
US4495168A (en) * 1983-08-22 1985-01-22 Basf Wyandotte Corporation Aerosol gel
US4814161A (en) * 1985-01-16 1989-03-21 Riker Laboratories, Inc. Drug-containing chlorofluorocarbon aerosol propellent formulations
US4704406A (en) * 1985-06-24 1987-11-03 Klinge Pharma Gmbh Sprayable pharmaceutical composition for topical use
US4755389A (en) * 1985-09-11 1988-07-05 Lilly Industries Limited Chewable capsules
US4857312A (en) * 1985-12-18 1989-08-15 Bayer Aktiengesellschaft Dihydropyridine spray, process for its preparation and its pharmaceutical use
US4689233A (en) * 1986-01-06 1987-08-25 Siegfried Aktiengesellschaft Coronary therapeutic agent in the form of soft gelatin capsules
US4863720A (en) * 1986-03-10 1989-09-05 Walter Burghart Pharmaceutical preparation and methods for its production
US4863970A (en) * 1986-11-14 1989-09-05 Theratech, Inc. Penetration enhancement with binary system of oleic acid, oleins, and oleyl alcohol with lower alcohols
US4919919A (en) * 1987-09-30 1990-04-24 Nippon Kayaku Kabushiki Kaisha Nitroglycerin spray
US5719197A (en) * 1988-03-04 1998-02-17 Noven Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
US5047230A (en) * 1988-07-08 1991-09-10 Egis Gyogyszergyar Aerosol composition comprising nitroglycerin as active ingredient
US5128132A (en) * 1988-11-22 1992-07-07 Parnell Pharmaceuticals, Inc. Eriodictyon compositions and methods for treating internal mucous membranes
US5605674A (en) * 1988-12-06 1997-02-25 Riker Laboratories, Inc. Medicinal aerosol formulations
US5766573A (en) * 1988-12-06 1998-06-16 Riker Laboratories, Inc. Medicinal aerosol formulations
US4935243A (en) * 1988-12-19 1990-06-19 Pharmacaps, Inc. Chewable, edible soft gelatin capsule
US5011678A (en) * 1989-02-01 1991-04-30 California Biotechnology Inc. Composition and method for administration of pharmaceutically active substances
US5186925A (en) * 1990-03-10 1993-02-16 G. Pohl-Boskamp Gmbh & Co. Nitroglycerin pump spray
US5240932A (en) * 1990-03-30 1993-08-31 Yasunori Morimoto Percutaneously absorbable compositions of morphine or analogous analgesics of morphine
US5428006A (en) * 1990-05-10 1995-06-27 Bechgaard International Research And Development A/S Method of administering a biologically active substance
US5143731A (en) * 1990-08-07 1992-09-01 Mediventures Incorporated Body cavity drug delivery with thermo-irreversible polyoxyalkylene and ionic polysaccharide gels
US5166145A (en) * 1990-09-10 1992-11-24 Alza Corporation Antiemetic therapy
US5135753A (en) * 1991-03-12 1992-08-04 Pharmetrix Corporation Method and therapeutic system for smoking cessation
US5290540A (en) * 1991-05-01 1994-03-01 Henry M. Jackson Foundation For The Advancement Of Military Medicine Method for treating infectious respiratory diseases
US5457100A (en) * 1991-12-02 1995-10-10 Daniel; David G. Method for treatment of recurrent paroxysmal neuropsychiatric
US5824307A (en) * 1991-12-23 1998-10-20 Medimmune, Inc. Human-murine chimeric antibodies against respiratory syncytial virus
US5364616A (en) * 1992-04-15 1994-11-15 The Procter & Gamble Company Use of H-2 antagonists for treatment of gingivitis
US5607915A (en) * 1992-09-29 1997-03-04 Inhale Therapeutic Systems Pulmonary delivery of active fragments of parathyroid hormone
US5981591A (en) * 1992-12-04 1999-11-09 Mayor Pharmaceutical Laboratories, Inc. Sprayable analgesic composition and method of use
US5725841A (en) * 1993-03-17 1998-03-10 Minnesota Mining And Manufacturing Company Aerosol formulation containing an ester-, amide-, or mercaptoester-derived dispersing aid
US5593684A (en) * 1993-08-04 1997-01-14 Pharmacia Ab Method and therapeutic system for smoking cessation
US6458842B1 (en) * 1994-02-01 2002-10-01 Knoll Aktiengesellschaft Liquid pharmaceutical compositions comprising thyroid hormones
US6706255B2 (en) * 1994-02-01 2004-03-16 Abbott Gmbh & Co., Kg Liquid pharmaceutical compositions comprising thyroid hormones
US5502076A (en) * 1994-03-08 1996-03-26 Hoffmann-La Roche Inc. Dispersing agents for use with hydrofluoroalkane propellants
US5645856A (en) * 1994-03-16 1997-07-08 R. P. Scherer Corporation Delivery systems for hydrophobic drugs
US5456677A (en) * 1994-08-22 1995-10-10 Spector; John E. Method for oral spray administration of caffeine
US5602182A (en) * 1995-01-30 1997-02-11 American Home Products Corporation Taste masking pseudoephedrine HCL containing liquids
US5908611A (en) * 1995-05-05 1999-06-01 The Scripps Research Institute Treatment of viscous mucous-associated diseases
US5635161A (en) * 1995-06-07 1997-06-03 Abbott Laboratories Aerosol drug formulations containing vegetable oils
US6299900B1 (en) * 1996-02-19 2001-10-09 Monash University Dermal penetration enhancers and drug delivery systems involving same
US5869082A (en) * 1996-04-12 1999-02-09 Flemington Pharmaceutical Corp. Buccal, non-polar spray for nitroglycerin
US5955098A (en) * 1996-04-12 1999-09-21 Flemington Pharmaceutical Corp. Buccal non polar spray or capsule
US6110486A (en) * 1996-04-12 2000-08-29 Flemington Pharmaceuticals Co. Buccal polar spray or capsule
US6271240B1 (en) * 1996-05-06 2001-08-07 David Lew Simon Methods for improved regulation of endogenous dopamine in prolonged treatment of opioid addicted individuals
US5891465A (en) * 1996-05-14 1999-04-06 Biozone Laboratories, Inc. Delivery of biologically active material in a liposomal formulation for administration into the mouth
US5795909A (en) * 1996-05-22 1998-08-18 Neuromedica, Inc. DHA-pharmaceutical agent conjugates of taxanes
US6143329A (en) * 1996-07-03 2000-11-07 Rorer Pharmaceutical Products Inc. Aqueous-based pharmaceutical composition
US6071539A (en) * 1996-09-20 2000-06-06 Ethypharm, Sa Effervescent granules and methods for their preparation
US6258032B1 (en) * 1997-01-29 2001-07-10 William M. Hammesfahr Method of diagnosis and treatment and related compositions and apparatus
US5906811A (en) * 1997-06-27 1999-05-25 Thione International, Inc. Intra-oral antioxidant preparations
US20040136914A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing ondansetron
US20050025713A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20060210484A1 (en) * 1997-10-01 2006-09-21 Novadel Pharma Inc. Buccal, polar and non-polar spray containing testosterone
US20060198790A1 (en) * 1997-10-01 2006-09-07 Dugger Harry A Iii Buccal, polar and non-polar spray containing ondansetron
US20030039680A1 (en) * 1997-10-01 2003-02-27 Flemington Pharmaceutical Corporation Buccal, polar and non-polar spray or capsule
US20030077229A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20030077228A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20030082107A1 (en) * 1997-10-01 2003-05-01 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20030095925A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20030095926A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030185761A1 (en) * 1997-10-01 2003-10-02 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20040141923A1 (en) * 1997-10-01 2004-07-22 Dugger Harry A. Buccal, polar and non-polar spray containing alprazolam
US20030190286A1 (en) * 1997-10-01 2003-10-09 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20030211047A1 (en) * 1997-10-01 2003-11-13 Indena S.P.A. Buccal, polar and non-polar spray or capsule
US6676931B2 (en) * 1997-10-01 2004-01-13 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule
US20040136913A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing sumatriptan
US20040062716A1 (en) * 1997-10-01 2004-04-01 Novadel Pharma Inc. Buccal, polar and non-polar spray of capsule
US20040120895A1 (en) * 1997-10-01 2004-06-24 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20040120896A1 (en) * 1997-10-01 2004-06-24 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US20060165604A1 (en) * 1997-10-01 2006-07-27 Dugger Harry A Iii Buccal, polar and non-polar spray containing sumatriptan
US20060159624A1 (en) * 1997-10-01 2006-07-20 Dugger Harry A Iii Buccal, polar and non-polar spray containing zolpidem
US20060222597A1 (en) * 1997-10-01 2006-10-05 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20060216240A1 (en) * 1997-10-01 2006-09-28 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US20050002867A1 (en) * 1997-10-01 2005-01-06 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20050025715A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20050025717A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20050025716A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20050025712A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20050025714A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20060216241A1 (en) * 1997-10-01 2006-09-28 Novadel Pharma Inc. Buccal, polar and non-polar spray containing diazepam
US20050142069A1 (en) * 1997-10-01 2005-06-30 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20050163719A1 (en) * 1997-10-01 2005-07-28 Dugger Harry A.Iii Buccal, polar and non-polar spray containing diazepam
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US6969508B2 (en) * 1997-10-01 2005-11-29 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US6998110B2 (en) * 1997-10-01 2006-02-14 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule
US6212227B1 (en) * 1997-12-02 2001-04-03 Conexant Systems, Inc. Constant envelope modulation for splitterless DSL transmission
US6375975B1 (en) * 1998-12-21 2002-04-23 Generex Pharmaceuticals Incorporated Pharmaceutical compositions for buccal and pulmonary application
US6816452B1 (en) * 1999-07-14 2004-11-09 Sumitomo Electric Industries, Ltd. Vehicle-to-roadside communication system, roadside communication station, and on-board mobile station
US6512002B2 (en) * 2000-01-12 2003-01-28 Pfizer Inc. Methods of treatment for premature ejaculation in a male
US20030191180A1 (en) * 2000-03-09 2003-10-09 Calvin Ross Pharmaceutical compositions
US7202233B2 (en) * 2000-03-28 2007-04-10 Farmarc Nederland Bv Alprazolam inclusion complexes and pharmaceutical compositions thereof
US20020102218A1 (en) * 2000-12-01 2002-08-01 Cowan Siu Man L. Stable, aerosolizable suspensions of proteins in ethanol
US20020110524A1 (en) * 2000-12-01 2002-08-15 Cowan Siu Man L. Method for stabilizing biomolecules in liquid formulations
US20070045229A1 (en) * 2002-03-11 2007-03-01 Keenan Joseph F System and method for the manufacture of surgical blades

Cited By (133)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090162300A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing alprazolam
US20060210484A1 (en) * 1997-10-01 2006-09-21 Novadel Pharma Inc. Buccal, polar and non-polar spray containing testosterone
US20030082107A1 (en) * 1997-10-01 2003-05-01 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20030095925A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030185761A1 (en) * 1997-10-01 2003-10-02 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20030190286A1 (en) * 1997-10-01 2003-10-09 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20040062716A1 (en) * 1997-10-01 2004-04-01 Novadel Pharma Inc. Buccal, polar and non-polar spray of capsule
US20030077228A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US9078816B2 (en) 1997-10-01 2015-07-14 Suda Ltd. Buccal, polar and non-polar spray containing ondansetron
US20050002867A1 (en) * 1997-10-01 2005-01-06 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20050025715A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20030077229A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20050025712A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20050025717A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US8236285B2 (en) 1997-10-01 2012-08-07 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US20100152262A1 (en) * 1997-10-01 2010-06-17 Dugger Iii Harry A Buccal, polar and non-polar spray containing ondansetron
US20100092403A1 (en) * 1997-10-01 2010-04-15 Dugger Iii Harry A Buccal, polar and non-polar spray containing zolpidem
US7632517B2 (en) 1997-10-01 2009-12-15 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US6998110B2 (en) 1997-10-01 2006-02-14 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule
US20050142069A1 (en) * 1997-10-01 2005-06-30 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US20050163719A1 (en) * 1997-10-01 2005-07-28 Dugger Harry A.Iii Buccal, polar and non-polar spray containing diazepam
US20050025713A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20090162298A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing sumatriptan
US20090123387A1 (en) * 1997-10-01 2009-05-14 Dugger Iii Harry A Buccal, polar and non-polar spray or capsule containing cardiovascular or reneal drugs
US6969508B2 (en) 1997-10-01 2005-11-29 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US6977070B2 (en) 1997-10-01 2005-12-20 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20090118170A1 (en) * 1997-10-01 2009-05-07 Dugger Iii Harry A Buccal, polar and non-polar spray or capsule
US20050281752A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20050281753A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule
US20050287075A1 (en) * 1997-10-01 2005-12-29 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20090162297A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing ondansetron
US20060222597A1 (en) * 1997-10-01 2006-10-05 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20060216240A1 (en) * 1997-10-01 2006-09-28 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US20060216241A1 (en) * 1997-10-01 2006-09-28 Novadel Pharma Inc. Buccal, polar and non-polar spray containing diazepam
US20060159624A1 (en) * 1997-10-01 2006-07-20 Dugger Harry A Iii Buccal, polar and non-polar spray containing zolpidem
US20060171896A1 (en) * 1997-10-01 2006-08-03 Dugger Harry A Iii Buccal, polar and non-polar spray containing alprazolam
US20060198790A1 (en) * 1997-10-01 2006-09-07 Dugger Harry A Iii Buccal, polar and non-polar spray containing ondansetron
US9078883B2 (en) 1999-10-29 2015-07-14 Recro Pharma, Inc. Treatment or prevention of hypotension and shock
US8470862B2 (en) 1999-10-29 2013-06-25 Recro Pharma, Inc. Treatment or prevention of hypotension and shock
US9446025B2 (en) 1999-10-29 2016-09-20 Recro Pharma, Inc. Treatment or prevention of hypotension and shock
US6919378B2 (en) * 2000-10-11 2005-07-19 Cephalon, Inc. Pharmaceutical solutions of modafinil compounds
US6977257B2 (en) * 2001-04-25 2005-12-20 Bristol-Myers Squibb Company Aripiprazole oral solution
WO2004035021A2 (en) * 2002-08-29 2004-04-29 Novadel Pharma Inc. Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
WO2004035021A3 (en) * 2002-08-29 2004-11-11 Novadel Pharma Inc Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20080213363A1 (en) * 2003-01-23 2008-09-04 Singh Nikhilesh N Methods and compositions for delivering 5-HT3 antagonists across the oral mucosa
US20100256210A1 (en) * 2003-01-23 2010-10-07 Singh Nikhilesh N Methods and compositions for delivering 5-ht3 antagonists across the oral mucosa
US20060062812A1 (en) * 2003-03-11 2006-03-23 Calvin Ross Novel compositions
WO2005032519A1 (en) * 2003-09-29 2005-04-14 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
JP2007507508A (en) * 2003-09-29 2007-03-29 ノヴァデル ファーマ インコーポレイテッド Oral polar and nonpolar sprays containing zolpidem
WO2005032517A1 (en) * 2003-09-29 2005-04-14 Novadel Pharma Inc. Buccal, polar and non-polar spray containing diazepam
WO2005030167A2 (en) * 2003-09-29 2005-04-07 Novadel Pharma Inc. Buccal, polar and non-polar spray containing alprazolam
WO2005030167A3 (en) * 2003-09-29 2006-04-13 Novadel Pharma Inc Buccal, polar and non-polar spray containing alprazolam
WO2005037193A2 (en) * 2003-10-03 2005-04-28 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor administered under hypothermic conditions for the treatment of ischemic mediated central nervous system disorders or injury
WO2005037193A3 (en) * 2003-10-03 2006-12-21 Pharmacia Corp Compositions of a cyclooxygenase-2 selective inhibitor administered under hypothermic conditions for the treatment of ischemic mediated central nervous system disorders or injury
WO2005046615A3 (en) * 2003-11-12 2006-06-22 Pharmacia & Upjohn Co Llc Compositions for treatment of central nervous system mediated disorders
WO2005046615A2 (en) * 2003-11-12 2005-05-26 Pharmacia & Upjohn Company Llc Compositions for treatment of central nervous system mediated disorders
US20100311718A1 (en) * 2004-01-30 2010-12-09 Astrazeneca Ab Treatment of Psychoses with Dibenzothiazepine Antipsychotic
US20050171088A1 (en) * 2004-01-30 2005-08-04 Astrazeneca Ab Treatment of psychoses with dibenzothiazepine antipsychotic
US20100291004A1 (en) * 2004-02-17 2010-11-18 Singh Nikhilesh N Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US7658945B2 (en) 2004-02-17 2010-02-09 Transcept Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US20050226925A1 (en) * 2004-02-17 2005-10-13 Transoral Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US20080008753A1 (en) * 2004-02-17 2008-01-10 Singh Nikhilesh N Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US7682628B2 (en) 2004-02-17 2010-03-23 Transcept Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US20080021016A1 (en) * 2004-03-12 2008-01-24 Levay Gyoergy Combined Pharmaceutical Composition for the Inhibition of the Decline of Cognitive Functions
US20100317694A1 (en) * 2004-10-19 2010-12-16 Krka, Tovarna Zdravil, D.D. , Novo Mesto Solid pharmaceutical composition comprising donepezil hydrochloride
EP2767163A1 (en) 2005-02-17 2014-08-20 Abbott Laboratories Transmucosal administration of drug compositions for treating and preventing disorders in animals
US20070287740A1 (en) * 2005-05-25 2007-12-13 Transcept Pharmaceuticals, Inc. Compositions and methods of treating middle-of-the night insomnia
US20070225322A1 (en) * 2005-05-25 2007-09-27 Transoral Pharmaceuticals, Inc. Compositions and methods for treating middle-of-the night insomnia
US20080057119A1 (en) * 2005-05-25 2008-03-06 Singh Nikhilesh N Compositions and methods for treating middle-of-the night insomnia
WO2006125774A1 (en) * 2005-05-25 2006-11-30 Janssen Pharmaceutica N.V. Pediatric formulation of topiramate
US20060276501A1 (en) * 2005-05-25 2006-12-07 Transoral Pharmaceuticals, Inc. Solid compositions for treating middle-of-the-night insomnia
US20060281783A1 (en) * 2005-05-25 2006-12-14 Transoral Pharmaceuticals, Inc. Compositions and methods of treating middle-of-the night insomnia
US8252809B2 (en) 2005-05-25 2012-08-28 Transcept Pharmaceuticals, Inc. Compositions for treating insomnia
US20100249177A1 (en) * 2005-05-25 2010-09-30 Singh Nikhilesh N Compositions and methods for treating middle-of-the-night insomnia
US20100249178A1 (en) * 2005-05-25 2010-09-30 Nikhilesh Singh Compositions and methods for treating middle-of-the-night insomnia
US8242131B2 (en) 2005-05-25 2012-08-14 Transcept Pharmaceuticals, Inc. Methods of treating middle-of-the-night insomnia
US20070066643A1 (en) * 2005-05-25 2007-03-22 Transoral Pharmaceuticals, Inc. Methods of treating middle-of-the-night insomnia
US20070123562A1 (en) * 2005-05-25 2007-05-31 Transoral Pharmaceuticals, Inc. Compositions and methods for treating middle-of-the-night insomnia
US20110039881A1 (en) * 2005-05-25 2011-02-17 Singh Nikhilesh N Compositions and methods for treating middle-of-the-night insomnia
US20070248548A1 (en) * 2006-04-19 2007-10-25 Blondino Frank E Stable hydroalcoholic oral spray formulations and methods
DE102006032427A1 (en) * 2006-07-13 2008-01-17 Neuraxpharm Arzneimittel Gmbh U. Co. Kg Use of composition comprising e.g. clozapine, quetiapine, olanzapine, benzyl- and/or phenylethyl alcohol, ethanol, ethereal oil, sweetener, and polyethylene glycol, for preparing an orally administering solution to treat schizophrenia
DE102006032426A1 (en) * 2006-07-13 2008-01-17 Neuraxpharm Arzneimittel Gmbh U. Co. Kg Use of a composition comprising e.g. clozapine and quetiapine; benzyl- and/or phenylethyl alcohol; propylene glycol; ethereal oil; and polyethylene glycol, for preparing an orally administering solution to treat schizophrenia
US20080081067A1 (en) * 2006-10-03 2008-04-03 Gupta Manishkumar Sustained release pharmaceutical compositions of venlafaxine and process for preparation thereof
US20080171089A1 (en) * 2006-12-22 2008-07-17 Blondino Frank E Stable anti-nausea oral spray formulations and methods
US20080280947A1 (en) * 2007-05-10 2008-11-13 Blondino Frank E Anti-insomnia compositions and methods
US20110040266A1 (en) * 2007-05-10 2011-02-17 Blondino Frank E Anti-insomnia compositions and methods
US20110086845A1 (en) * 2007-07-10 2011-04-14 The Board Of Trustees Of The University Of Illinois Compositions and Methods for Treating Neurodegenerating Diseases
US8580776B2 (en) 2007-07-10 2013-11-12 The Board Of Trustees Of The University Of Illinois Compositions and methods for treating neurodegenerating diseases
US20090107836A1 (en) * 2007-10-30 2009-04-30 Novellus Systems, Inc. Closed Contact Electroplating Cup Assembly
US20100196286A1 (en) * 2008-12-01 2010-08-05 Armer Thomas A Inhalation delivery methods and devices
US20100192945A1 (en) * 2008-12-23 2010-08-05 Robert Owen Cook Inhalation devices and related methods for administration of sedative hypnotic compounds
US9161912B2 (en) 2008-12-23 2015-10-20 Map Pharmaceuticals, Inc. Inhalation devices and related methods for administration of sedative hypnotic compounds
US8555875B2 (en) 2008-12-23 2013-10-15 Map Pharmaceuticals, Inc. Inhalation devices and related methods for administration of sedative hypnotic compounds
EP2429521A2 (en) * 2009-05-15 2012-03-21 Recro Pharma, Inc. Sublingual dexmedetomidine compositions and methods of use thereof
US20110021588A1 (en) * 2009-05-15 2011-01-27 Recro Pharma, Inc. Sublingual dexmeditomidine compositions and methods of use thereof
EP3305281A1 (en) * 2009-05-15 2018-04-11 Recro Pharma, Inc. Sublingual dexmedetomidine compositions and methods of use thereof
EP2429521A4 (en) * 2009-05-15 2013-08-21 Recro Pharma Inc Sublingual dexmedetomidine compositions and methods of use thereof
US20110124656A1 (en) * 2009-11-20 2011-05-26 Tonix Pharmaceuticals, Inc. Methods and Compositions for Treating Symptoms Associated with Post-Traumatic Stress Disorder using Cyclobenzaprine
US9918948B2 (en) 2009-11-20 2018-03-20 Tonix Pharma Holdings Limited Methods and compositions for treating symptoms associated with post-traumatic stress disorder using cyclobenzaprine
US10722478B2 (en) 2010-06-24 2020-07-28 Tonix Pharma Holdings Limited Methods and compositions for treating fatigue associated with disordered sleep using very low dose cyclobenzaprine
US9474728B2 (en) 2010-06-24 2016-10-25 Tonix Pharma Holdings Limited Methods and compositions for treating fatigue associated with disordered sleep using very low dose cyclobenzaprine
US9585893B2 (en) 2011-02-23 2017-03-07 Coeruleus Ltd. Flumazenil complexes, compositions comprising same and uses thereof
EP2526925A1 (en) 2011-05-23 2012-11-28 Deva Holding Anonim Sirketi A dose adjustable oral pump spray or aerosol spray containing memantine
US9795559B2 (en) 2011-12-11 2017-10-24 Recro Pharma, Inc. Intranasal dexmedetomidine compositions and methods of use thereof
US10682311B2 (en) 2011-12-11 2020-06-16 Baudax Bio, Inc. Intranasal dexmedetomidine compositions and methods of use thereof
WO2013188847A1 (en) 2012-06-15 2013-12-19 Tonix Pharmaceuticals, Inc. Compositions and methods for transmucosal absorption
EP2861223A4 (en) * 2012-06-15 2016-01-27 Tonix Pharmaceuticals Inc Compositions and methods for transmucosal absorption
CN104684550A (en) * 2012-06-15 2015-06-03 通尼克斯制药有限公司 Compositions and methods for transmucosal absorption
CN111388430A (en) * 2012-06-15 2020-07-10 通尼克斯制药控股有限公司 Compositions and methods for transmucosal absorption
TWI642429B (en) * 2012-06-15 2018-12-01 托尼克製藥有限公司 Compositions and methods for transmucosal absorption
TWI683660B (en) * 2012-06-15 2020-02-01 美商托尼克製藥有限公司 Compositions and methods for transmucosal absorption
CN109106697A (en) * 2012-11-09 2019-01-01 丝维塔斯治疗公司 The high dose levodopa capsule used for lung
US10322094B2 (en) 2013-03-15 2019-06-18 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US11737991B2 (en) 2013-03-15 2023-08-29 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US11839594B2 (en) 2013-03-15 2023-12-12 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US10117936B2 (en) 2013-03-15 2018-11-06 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US9956188B2 (en) 2013-03-15 2018-05-01 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US9636408B2 (en) 2013-03-15 2017-05-02 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US10736859B2 (en) 2013-03-15 2020-08-11 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US10864175B2 (en) 2013-03-15 2020-12-15 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US10864176B2 (en) 2013-03-15 2020-12-15 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride
US11026898B2 (en) 2014-09-18 2021-06-08 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride
US10357465B2 (en) 2014-09-18 2019-07-23 Tonix Pharma Holdings Limited Eutectic formulations of cyclobenzaprine hydrochloride
US11826321B2 (en) 2017-12-11 2023-11-28 Tonix Pharma Holdings Limited Cyclobenzaprine treatment for agitation, psychosis and cognitive decline in dementia and neurodegenerative conditions
CN109010323A (en) * 2018-08-27 2018-12-18 北京普瑞博思投资有限公司 Molten film of rivastigmine-hydrogentartrate mouth and preparation method thereof
US11433046B2 (en) * 2019-12-10 2022-09-06 Tulex Pharmaceuticals Inc. Compositions and methods for treating epilepsy, seizures and other conditions
US11633374B2 (en) 2019-12-10 2023-04-25 Tulex Pharmaceuticals Inc. Compositions and methods for treating epilepsy, seizures and other conditions
US11826343B2 (en) 2019-12-10 2023-11-28 Tulex Pharmaceuticals Inc. Compositions and methods for treating epilepsy, seizures and other conditions
US11911362B2 (en) 2019-12-10 2024-02-27 Tulex Pharmaceuticals Inc. Compositions and methods for treating epilepsy, seizures and other conditions
CN112390767A (en) * 2021-01-19 2021-02-23 嘉实（湖南）医药科技有限公司 Preparation method of eperisone hydrochloride impurity F

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US6977070B2 (en) 2005-12-20
EP2283814A1 (en) 2011-02-16
JP2006505569A (en) 2006-02-16
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CA2497262A1 (en) 2004-04-29
EP2283814B1 (en) 2012-09-19
EP2283813B1 (en) 2012-09-19
US20040120895A1 (en) 2004-06-24
EP2277506A1 (en) 2011-01-26
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EP2283815A1 (en) 2011-02-16
EP2283813A1 (en) 2011-02-16

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