CA2259526A1

CA2259526A1 - Nonocclusive drug delivery device and process for its manufacture

Info

Publication number: CA2259526A1
Application number: CA002259526A
Authority: CA
Inventors: Gastone P. Bello; John W. Lyle; Donald A. Johnson
Original assignee: Individual
Current assignee: U S Dermatologics Inc
Priority date: 1996-07-03
Filing date: 1997-07-02
Publication date: 1998-01-08
Also published as: US5891463A; AU3718797A; EP0910352A2; WO1998000117A3; US5716621A; JP2000514063A; WO1998000117A2

Abstract

A nonocclusive drug delivery device includes (a) an open cell, flexible, oleophilic thermoplastic resin foam layer, (b) a substantially moisture vapor permeable, liquid impermeable, flexible thermoplastic barrier layer bonded to the upper surface of the foam layer, (c) a pressure sensitive adhesive layer and (d) a drug composition comprising a drug and an oleophilic drug delivery vehicle.

Description

NONOCCLUSIVE DRUG DELIVERY DEVICE
AND PROCESS FOR ITS MANUFACTURE
s BACKGROUND OF THE INVENTION
This invention relates to a nonocslllcive drug delivery device and to a method for its rn~mlfartllre.
One known type of tr~ncderm~l drug delivery device, also variously 10 referred to as a m~Ai~l bandage, tre~tm~nt pad, drug patch, e~c., incl~de~ a drug depot, or reservoir, in the forrn of a drug-storing matrix or carrier and an adhesive for att~chine or securin~ the device to a surface of unbroken skin.
In one particular type of construction, a known drug delivery device is provided as a l~ n~e of a therrnoplastic microcellular foarn layer carrying a 15 measured quantity of drug or drug-con~ining composition, the upper surface of the foam layer being bonded to a thermoplastic film barrier layer and its lower surface po~.cessing a contact adhesive. It has been found that a drug delivery device of this general construction may be liable to one or more drawbacks which preclude its effective use and practical acccptancc. Por example, unless the peel ~cllgth of the 20 device is signific~ntly less than the strength of the bond between the foam and barrier layers, on peeling the device from the skin, separation (i..e, del~min~tion) of the foam and barrier layers may occur with portions of foam continning to adhere to the skin. Another problem can arise when, due to the physico~hemical nature of the foam and the drug or drug-cont~ining composition, the latter migrates into the 25 adhesive thereby impairing the strength of the bond by which the device is held to the skin.

. , _ . . _ .

SUMMARY OF THE INVENTION
In accordance with the present invention, a nonocchlsive drug delivery device is provided which co~ .ises:
a) an open cell, flexible, oleophilic thermoplastic resin foam layer 5 possessin~ upper and lower surfaces and predetPrmin~ adhesive, drug depot and drug migration barrier zones;
b) a s~1bst~nti~lly moisture vapor permeable, liquid imperme~le, flexible thermoplastic barrier layer bonded to the upper surface of the foam layer, the composite of the barrier and foam layers posseccing a moisture vapor tr~ncmi.~sion rate of at least about 500 glm2124 h at 100% r.h and 32~C, the bond strength between the barrier layer and the foam layer being such as to resist separation of the barrier layer from the foam layer when the drug delivery device is subjected to the flexing and/or stretching forces normally enco~ d during its useful applied life;
c) a plc;s~le sensitive adhesive within the adhesive zone of the 15 foam layer, the adhesive layer imparting a peel strength to the drug delivery de~rice which is sufficiently below that of the bond strength between the foam layer and the barrier layer such that upon peeling the device from the skin, substantially all of the foam layer remains bonded to the barrier layer; and, d) a drug composition con~plisi~lg a therape~ltir~lly effective 20 amount of at least one drug in an oleophilic drug delivery vehicle, the drug composition being contained within the drug depot zone of the foam layer and separated from the adhesive zone by the barrier zone.
The foregoing drug delivery device effectively overcomes each of the above-noted drawbacks associated with the prior art drug delivery device. Thus, the 2~ device of this invention resists tlel~min~tion when pulled from the skin and since its drug-con~ining component remains isolated from the adhesive component by a barrier zone, there is little, if any, likelihood of the drug composition re~rlling the adhesive and impairing its effectiveness.

WO 98J00117 PCI'/US97/11275 ~RIEP DESCRIPTION OF THE DRAW~NGS
~ig. 1 is a cross-sectional view of one embo-lim~nt of a drug deliYery device in accordance with the invention;
Figs. 2A-E sch~m~tic?lly illustrate the y~ulcipal stages in the S m~mlf~tllre of the drug delivery device of Fig. 1;
Fig. 3 and 3A illustrate the front and reverse sides of another embo-lim~nt of a drug delivery device herein provided as a facial mask for delivering one or more derm~ologically and/or cosmetically beneficial active agents to facial skin; and, Fig. 4 illustrates another type of facial mask assembled in situ from several units of the drug delivery device of this invention each having its own configuration.

DESCRIPTION OF THE PR~FERRED EMBODIM~NTS
One embodiment of a nonocclusive drug delivery device in accordance with this invention is shown generally in Fig. 1 at 10. The drug delivery deviceincludes a subst~nti~lly moisture vapor perrneable, liquid ilnpe~ eable, flexible thermoplastic barrier layer 11 bonded to, and generally coextensive with, upper surface 12 of open cell, flexible, oleophilic thermoplastic resin foam layer 13.Ple~ re sensitive adhesive 14 occupies a zone, or stratum, 15 on lower surface 16 of foam layer 13 for securing the drug delivery device to the skin. Drug composition 18 occupies drug depot zone 19 and is separated from adhesive zone 15 by barrier zone 20 which prevents or inhibits migration of the drug composition into adhesive 14. A
release liner 17 seals and protects lower surface 16 of the foam layer during the residency of drug delivery device 10 within its package.
The mi~ -,. strength of the bond between barrier layer 11 and foam layer 13 is one of several critical requile.l,e~ of the drug delivery device of this invention and must be sufficient to prevent or inhibit separation, i.e., del~min~ion, of the barrier layer from the foam layer under the sort of flexing and/or stretching forces that may be encountered curin~, the uscful life o' the a~)plied d~vic~. In gener~l, bond strengths of at least about '~ newtons (~), preferably at least about 3 N and more preferably at least bout S ~ ~vill generally provide satisfactory results in LhiS regard However the bond berween layers 11 and 13 may be achieved, it is necessarv Lhattl'le S bond itself not result in I significant rec'uction in the moisture vapor transmission r~te (~IVTr~ of the assembled layers ~'hi!e .~nown and convenlional contac; adhesivescan re~di'v r,.ovide barr:er layer-to-foarll lay~r bond strengths of 2 ~ and gre2[er, they ma- be disadvar.tageous in .educing ~,e ~IVTR of the assembled layers to anunaccept~ble degree A~cordingl~r, it is pret'er;-ed herein to emplov a nor~dhesive 10 bonding tec~Lique, e ~, one err.ploving '.~eat such as ~ rne bon~ling that is caFabl~ of producing the desired bond strengths but wilhout signif;can~lv reducing the ~ TR ot the ccmpcsite forrned from layers 11 ar.d 13 In genera., the ~IVTr~ or' ~'~e '~arrier l~yer-t'oam laver sub~ssemblv will be at leasl about 5Q0, prefer-bl~ at le-~st about 1000 ancl more pref.erablv a~ le:~st about 1~C0, glm~ h at 100C~o r h and ~''CC as measured b,v AST~I Fi2-.9-90 Ar.other crilical reauiremen.t o.' ~.e dnig delivery device of ~s invenlicn is that whalever the bcnd stren~t~h celween barrier layer 11 and foam laver 13, t~.e conlact adhesive must impart a peel slrength to the drug delivery device. i e, the amoun.t of force req ~ired to peel the sper.t drag delivery device from the slcin, 20 ~vhich is less, preferablv at least about ~0 percent less and more prefer~bly at least ~bout ~0 percent less, than such bond slr~ h in order to prever.t or rrlinirnize the separation of the barrier layer from the fo~m ilver ~vhen the sper.t drug delive.
device is peeled from the skin.
Barrier layer 11 can be any therrnoplastic film possessing an ~ 'TR of 25 one of the aforestated values. Preferably, tl~.e barrier layer can be a pol~urethane filrn possessing an averane Ihickness of from about 0.5 to about 3 5 mils and preferablv ~ o.oo~ 5~) (0.00381~ (c~vl~ (Ir5.~ 1~3/C~J
from about 1.0~,to abou~ 1.51mils~and a tensile strength of at least about 2500 psiland preferably at least about 3500 psi,~( ~'G l AM~NDED S~l~ET
,L

-__ CA 022S9C.26 1998-12-30 Fog8/00ll7 ~ ;~ PC-I,US97/11275 Fo~m layer 1~ in its ,~s-manufactured st~te is an open ce!l, fle.Yible, ol~ophilic foam t~.at pro~id~s a stable rnatri.Y for th~ c~rl~ ~nd its oleophilic deliver,~
~chicle. By '!stable ~r.atri~" is meant that property of the foam ~vhic~, o~ing to its o!eo~hilic ch~racte-. enables the foam to ~ur.ction nol onl,v as a depot, or reservoir, ror th~ ol o?hilic cim ~ composi~ion, but ccnfir.es the composition tQ zon 1~ hich is se?arated by barrier zone ~0 t'rom zone l~ occupied by pressure sensiti~e adhesive li',. Thus. the oleopi~ilic char2cteristics of the foam layer prevent or inhlibit rni(7ration of the dru~ composi~ion into adhesive zone l~ ~vhere it could destrov or irr.?air the cffectiveness of achesive 1', in securing t;~e drug delivery device to the s~in. Another adv2n~ag~eous charac erislic of the drug deliver,v device herein is ils abili~ to maint.~in continuous contacr be~ween the dr.là composition and the s~in thus assuririr that the drug will be constar.tly available at the site of its administration. (/ ', ~) In ~veneral Lhe useful foams possess a density of from about 0.8~to J ~ 9~ (~ d~
about ~.Oland ~,~referably from abqut 1.21to about 4.~l1b/ft,/a number ot pores ~cer inchlof frcm about ~Olto about 120l2nd preferably from about 60lto about 90l and can be ~ull~ or partial!v reticulated or nonreticulate(l. Th~e average Lhickness of Lhe foam ( o. o ~ r6) ( O - S't) f ~
lave. c~n varv from ab(out ~ Olto apou~100lmils~a)nd for many a?plications is preferabl- from abo ~t 40llo about 70 mils~Suitable fo~ms thal c~n be employed he-ein include the u:atre~ted oleophilic (i.e, hydrophobic) open cell pol~uretr.ane fo~ms disclosed in IJ.S. Pa~ent No. 5,~5'~,711, the contents of ~~hich .?"'' incorporatad by refe-~nce herein.
Pressure sensitive adhesive 14 can be selected from an~ of Lha k~own and conventional medical grade adhesives, e.g., those based on polvacr,vlic~
polyvinylether, or polvurethane resir,s. It is an essential requirement that ~he amount of adhesive 14 applied to zone 15 of foam layer 13 be suff'lcient to achieve an acceptable level of adhesion of drug delivery device 10 to the s~in but, as previously stated, ~,vith a resulting peel strength that is sufficiently below the bond strength between the barrier and foam layers. The amount of adhesive that will satisfy these criteria can be readily derermined by simple and routine testing. Ordinari!y, a -5 A,~ la~ J~EI

WO 98/OOlI, ~ PCT/IJS97/11''75 medical grade polyacrylic ~ si-e suc,~l as Durot~ (Nation~l St~rvl~ Ch~mical Company, Brid~e~vater, NJs) or Gelva~ (~Ionsanto Inc., St. Louis, ~IO) applied to a ~ O.c~)~ J (o oo~ crt~J ~ o5~,) thickness of fror.-. about l!to about 3.~'mils and pr_ferably from abcut '.Olto about ( 0 o o ~
~ mils~,(depend ng, of course, on the thic~ness of the ro~rn layer), or applied al a S rate of from about ~ to about 100 nicrn- and preferably from about 50 ~o about 6 g/cm-. udll meet these requiremen~s reasonably well.
A process for manufacturing the drug deliverv devic- of r~r,is in-ention is schem~tica!ly illustrated in Figs. ~A-E.
As sho~vn in Fig. ~.~, barrier layer 11 is bonded to upper sur.ace 1~ of foam laye. 13 employing a suitar!o bonding technique, preferably, ~ rl?~-ne bonding procedure for the reason stated above. Flame bor,ding, or fi2me l~rnination, thedetails of ~hich are ~vell ~r.o~vn, invol-es Ihe superficial softcninv~ or r.oltin_ of upper surface 1~ of foa-n layer 13 and while surfac_ 12 is in this state, uhe applicalion of barrier layer 11 meroto Conditiors of the flame bonding operatior. inc.ude the ternpervqture of ~he flvame, the proximity of surface 12 of the foarn ~o ~.e ~la~e and the duration of exposure of uhis surface to L~e flame. The conditions LLat v!e emploved for a pa-ticul.r fl.~me bonding operation will depend on uhe prop~r~les cf ul~.e foarn and barrier l,qyers, the bond strerlgth desired and simil.qr fqctors of ~,hich uh~ose s~illed in the art ~re aware. For the preferred polyurethane barrior f1lm and pol~reth,qne foam components, a flame tempe.qture of frorn about lS00 to about ~00~C. 2 distance from ~he flame to the upper surface of the foam of up to about ~ c~. ar.d an exposure time of such surf~ce of from abou~ ~5 to about ~0 milliseconcls ~vii! usuqlly provide the desired minimum bond strengths or better.
In another type of nonadhesive bonding procedure, vacu1~n lamination, a vacuum is appliecl to the lower surface of the foam layer and a molten thermoplastic I,qyer intended to provide the barrier layer is cast upon the uppe- surf~c. of the foam la,ver. The vacuum partially draws the cast layer of molten resin into the structure of the foam so that when the resin cools and solidif1es, it provides the barrier layer securelv bonded to the foam layer.

-6- A~AENCE0 In Fig. 2B, the barrier layer/foam layer composite has been inverted (its orie,ltation for ~is and the rern~inin~ operations shown) and a first, or temporary, release liner 30 with mçtlical grade adhesive 14 applied thereto is brought into contact with zone 15 of lower surface 16 of foarn layer 13. As shown in Fig. 2C, release5 liner 30 possesses cut-out portion n providing an openi"g, or "windown, through which drug composition 18 is applied to exposed drug depot zone 19 of foam layer13. Drug co"~osilion 18 is applied in a fluid or semi-fluid state which, e.g., can be achieved, by heating, so ~at the composition spreads out somewhat from its initial point of application to zone 19. However, after rear~ the maximurn extent of its10 spread and hardening, drug co"-~osition 18 will be ~u~vunded by barrier zone 20 lying between it and zone 15 through which contact adhesive 14 has infiltrated.
A large variety of drug-cont~inin~ compositions can be incorporated into the drug depot zone of foarn layer 13 of drug delivery device 10. The term "drug" is used herein in its broadest sense as referring to any subst~nre or 15 composition possessi.~ t}.eL~l e~ r~lly or me~licin~lly beneficial activity and includes yrescliytion and nonplesc,iytion ph~rmareutir~ls, rne-lirin~ls, mp~ic~m~nt~ active ingredients of cosmetic and personal care preparations, and the like. Specific drugs that can be incorporated into drug composition 18 include topically delivered local ~nPsthetics such as be~7oc~inr~ procaine hydrochloride, tetracaine, tetracaine 20 hydrochloride, dibucaine, lidocaine, lidocaine hydrochloride, bupivicaine, dyclorun, etidocaine, mepivicaine, butamen picrate, ~imethicoquin hydrochloride, cyclomethylcaine sulfate, and the like; analgesics and anti-infl~mm~ory agents such as buprenorphin, butophanol tartrate, a~etaminophen, fentanyl, mefenamic acid, fl~lten~mic acid, diclofenac, oxyphen~-l~zonc, phenyb~l~zone, ibuprofen, 25 flurbiprofen, naproxen, menthol, methyl salicylate, phenol, salicylic acid, benzyl alcohol, camphor, c~mphorated metacresol, juniper tar, resorcinol, allyl isothiocyanate, c-aps~irin~ and the like; corticosteroids such as alclometasone ~iipropionate, ~mr.inoci(le~ hydloco.lisone, bet~mrth~cone dipropionate, bel~...fth~cone valerate, deso~tim~a~one, clobetasol propionate, flurandrenolide, halcinonide, CA 02259526 l998-l2-30 WO 98100~17 halobetasol, estradiol, testosterone, proge;,L~,o~le, flulir~col~r~ clobetasol, lex~m~th~cone, dexonide, fluocinolone acetonide, flucir10r-il1e, medroxyl,rogest~"o,le, o...P~sone furoate, tri~mrinrJlone~ and the like; antibiotics such as bacitracin, bacitracin zinc, chlortetracycline hydrochloride, chlorhex~dine glucorrte, 5 clindamycin, cliquinol, neomycin sulfate, polymyxin B sulfate, erythromycin, ger-t~micin, s~11fathi~70le, sl-lf~ce-Amide, su1f~ben7~mi~le, oxytetracycline hydrochloride, tetracycline, and the like; antimicrobial agents such as be~7~1konium chloride, chlorh~ lin.o gl~1corl~te, hexaclorophene, mafenide acetate, nitrofurazone, nystatin, acetos~1fAmin.o, clortrimazole, povidone-iodine, and the like; antifungal 10 agents such as amphotericin B, butoconazole, cetylpyri~1ini-~m chloride, chlorxylenol, cyclopirox olamine, clioquinol, clotrimazole, sulconazole nitrate, nystatin, oxyconazole, econazole nitratc, ketoconazole, miconazole nitrate, naftifine hydrochloride, pe~ .ycin, pyrrolinitrin, terbinafine, triacetin, and the like; debriding agents such as deoxyribonuclease, collagenolytic, debridem~nt~ fibrinolytic or 15 proteolytic enzymes, papain, papain-urea, and the like; AntihictAmin~s such as chlorcyclizine hydrochloride, diphenylhydramine hydrochloride, tripc1en~-~...i..r hydrochloride, and the like; antiepileptics such as nitr~7ep~m, meprobamate, clollazeparn, and the like; coronary v~co~ tors such as nitroglycerine, dipyridamole, erythritol, tetranitrate, pentaerythritol te~anitldte, propatylnitrate, and the like;
20 ~1erm~tologicals such as retinal, retinol, retinoic acid and their derivatives, hydroxyacids, a1ph~krtoacids, and the like; and other dn~gs such as benzoyl peroxide, podofilox, masoprocol, nicotine, scopolamine, nitroglycerine, fluorouracil, hydrocolloids, hydroquinone, monobenzone, tretinoin and acyclovir.
These and other drugs are provided in some suitable diffusable 25 oleophilic m~--linm, e.g., an ointrnpnt~ paste or other oleophilic vehicle, in accordance with known established pharrn~relltic~l fo~ tin~ practice. In those cases where rapid penetration of the drug is desired, it may be advantageous to include one or more pen~t~dtion e~h~nrers in the diffusable drug composition. Tnrluded among the penetration enh~nrers that can be used herein are butylene glycol, capric acid, caproic PCI~/US97/1 1275 acid, caprylic acid, caprylic/capric ~iglyceride, diethylene glycol, diethylene glycol monoethyl ether, glycerin, glyceryl dioleate, glycerol monooleate, glycerol trioleate, hexylene glycol, isopropylmyristate, isopro~ylp~lmit~te, linoleic acid, methyl laurate, oleic acid, oleyl alcohol, polyethylene glycol 200, polyethylene glycol dilaurate, S propyl oleate, propylene glycol, sq~ n~, and the like.
In Fig. 2D, temporary release liner 30 is removed leaving adhesive 14 to remain incorporated in zone 15 of foam layer 13. T~en, as shown in Fig. 2E, second, or final, release liner 40 is applied to lower surface 16 of the foam layer where it remains until such time as drug delivery device 10 is to be applied. If10 desired, drug delivery device 10 can be trimm~ e.g., along line 25.
Drug delivery device 10 can also be fabricated by applying adhesive directly to the adhesive zone of the lower surface of the foasn layer in the barrier layer/foam layer composite and, following the evaporation of any solvent with which the adhesive may be fonmll~te~l, applying the drug composition to the drug depot15 zone of the foam layer. This procedure lends itself to a continuous or semicontinuous m~n~f~etllring operation, e.g., feeding the barrier layer/foam layer composite in the form of a contimlol1s or lengthy strip to an adhesive coating head where the adhesive is applied, passing the coated strip through an oven to accelerate evaporation of the solvent present in the adhesive, incoll~ol~ting the drug into the drug depot zone, 20 applying a final release liner and cutting the strip into individual drug delivery device units of desired length.
Drug delivery device lO can be manu~actured in a variety of sizes and shapes and can be planar or three-dimensional. Figs. 3 and 3A illustrate front and reverse views 40 and 50, respectively, of single piece facial mask 30 constructed in 25 accordance with the present invention. Mask 30 can either be m~mlf~ctllred as an entirely planar unit or it can be forrned, e.g., by vacuum mokling or casting, into a unit shaped to fit the contours of the face. Contact adhesive 51 can be applied not only to an adhesive zone defined along the perimeter of the mask but to one or more additional locations to promote a more secure ~ttachment of the mask to the face.

WO 9~1100117 PCI'/US97/11275 Dmg depot zone 52 can be filled with any one of several known and conventional drug compositions for treating dermatological disorders or improving cosmetic conditions such as dry skin, acne, keratoses, psoriasis, ec7~ , pruritus, age spots, lertigines, me!~sm~c, wrinkles, warts, blemi~h~s~ l~pe.~ nt~1ion, infl~mm~tory S derm~toses, skin ch~nges associated with aging, etc.
Pig. 4 i~ tr~tes in front view another type of facial mask 70 made up of several el~ nl.~; 71-74 each possessing, as shown in the cut-away view of elern~nt 74, the cons~uction of drug delivery device 10. Flf~ c 71-74 can be separated from each other (as shown) or they can be made to slightly overlap to provide more complete coverage. As in the case of facial mask 30 of Pig. 3, mask 70 can contain one or more dermatologically or cosm~tically active agents for the tre~tm~t of facial shn.
The following examples illustrate drug delivery devices within, and for comparison purposes, outside the scope of the invention.

~ CA 022S9526 1998-12-30 ~vo 98/00117 .JrT,uss7!1127S

E~rnpl~s 1-3 ComDarati~e E~amrL71es ;-~
These e~amples illustrate tr.e efrects of usin~ adhcsivcs and nor.-adheslve bonding on the ~IVTRs of the barrier ti!m comporlents oi~' severai dr;~deliverr devices. Thr resi'ts are sllO~lliII Table 1.

Tahle 1 Effects of Bondinri Techniaue ~ ~IVTR

~ 'v'TR o~
~IVT~ B2.rierPDr~Drt B~rr~r o.~ L~ or.
L~ve. Bondin~, L~ r.i.n;~t.cn BarrlDr Fo~rn L~-e ~Inr.ols~) (rni!~) (c,~1,) TDrhr~ia~o L~erC~imrosl D ~ TR

Control 1 5 (oooi~ ~or.e lOS0 Comp E.~ coirj Pol~crvl c 690 - ~6 .~dhesive-, I mii'~~~'S~
Com? E.~ ~ ' 5 '~ ~~j~ Polv~crvli~ 470 AdhDsive', 3 mils ( o.~o ~6 c~
Corr.r~ E~ 3 1 5-oCO~J Adhesive' <l mii 810 - ~' E.~ 1 1 0 (o ~ Fiame (~OOl~c~) 13l5 11~0 'S
E.~; ~ 1 5(ooo~) Fla.nD 10S0 1''~ a~
EY ~ cco~ V~cuum L~r.in~!ion 1100 !~7 '~S
-'Pol,~re!h~ne film.
'Gel-a~ (Monsar.to Inc ) 3Tvcel8 (Lord CorI3 Industri~l Coati~g Div, Er~e, PA) These data show that the use of adhesives resulted Lr. rel;ll.vel.~ large reductions in the MVTR of Lhe uncoa~ed barr!er layer film. Thus, each of ~hree separate applications of adhesive (Corr.parative E~amples 1-3) reduced t~ie ~vfVTR of the control barrier layer by 36, 55 and ~5 percent, respectively. The use of flame bonding and vacuum laminalion, in contrast, had considerably less adverse effect on ~IVTR and in the barrier layerlfoam layer composite of E~ample 2, ac~ually provided a 16% increase in ~VTR.

-11- A~ C~-J S ~

E,Yan ple 4 C~mp~-~ t;~ e F,~ mples ~' an~ 5 These e,Yamples iilustrate the relationship of the strength of the bond between the barrier laver ~nd the foam layer and peel strength. The results 'lre se~
5 forth in Table ~.

Table ': Rel;ltionship of Barrier Layer-Foam l aver B( nd ~Strenoth and Peel Stren~th Bor.d Strength Perce.rlt By Which Bet~een E3.1rrie~.' Peel Strenttl. Peel Strength Fo~m L~ver (from Stair,les:i Is Less Th~n E.ctentct Comoo~site. ~ ~i;eel~ ~' Bor.d Stren~!h Delaminatior~
1~
Corr~p E.~ .1 0 Fo~m l~er entl.e!,v del~rnin~ted Com?. E,~. 5' 3.7 ~.6 ~0 Fo~m l~er ?ar.iaii-del~ninated E.~;. 1' 5.6 ~.9 4~ Foam !a~cr remained corr,pletely Donc~d to the ~ar ier iaver (3 ~ /n J ~~ oo~cr~
l~onre.ic~lateci ?oi-~urethane foam, ~ Ib!~ on 1.~ mil~polyurethane uarrier film, ;-:t'~. I rr.il contac~ adhesive (~k~/m3~ ~o oo~ 20 ~Retic~ ted polv~rethane to~m. ~ Ibift'¦, on 1.5 mii~polyL rethane bar. er t~ ith 1 m i contact adhesive ~ /' As these d..~,~ sho~v, for the particular druo deliver,v devices tested the peelstrength needed to be nearly half that of the bond strength for the fo~,rn lave. to remain completely bonded to the barrier layer. 25 I ~r~
~NI~N~E~ Srl~tl -

Claims

WHAT IS CLAIMED IS:

1. A nonocclusive drug delivery device which comprises:
a) an open cell, flexible, oleophilic thermoplastic resin foam layer possessing upper and lower surfaces and predetermined adhesive. a drug depot zone and a drug migration barrier zone separating the adhesive from the drug depot zone;
b) a substantially moisture vapor permeable, liquid impermeable, flexible thermoplastic barrier layer bonded to the upper surface of the foam layer, the composition of the barrier and foam layers possessing a moisture vapor transmission rate of at least about 500 g/m2/24 h at 100% r.h. and 32°C the bond strength between the barrier layer and the foam layer being such as to resist separation of the barrier layer from the foam layer when the drug delivery device is subjected to the flexing and/or stretching forces normally encountered during its useful applied life;
c) a pressure sensitive adhesive within the adhesive zone of the foam layer, theadhesive layer imparting a peel strength to the drug delivery device which is sufficiently below that of the bond strength between the foam layer and the barrier layer such that upon peeling the device from the skin, substantially all of the foam layer remains bonded to the barrier layer; and, d) a drug composition comprising a therapeutically effective amount of at least one drug in an oleophilic drug delivery vehicle, the drug composition being contained within the drug depot zone of the foam layer and separated from the adhesive by the barrier zone.

2. The drug delivery device of Claim 1 wherein the foam layer and the barrier layers are each fabricated from a polyurethane resin.

3. The drug delivery device of Claim 1 wherein the MVTR is at least about 1000 g/m2/24 h at 100% r.h. and 32°C.

4. The drug delivery device of Claim 1 wherein the bond strength between the barrier layer and the foam layer is at least about 2 N.

5. The drug delivery device of Claim 1 wherein the bond strength between the barrier layer and the foam layer is at least about 3 N.

6. The drug delivery device of Claim 4 wherein the peel strength of the device is at least about 20 percent less than the bond strength between the barrier layer and the foam layer.

7. The drug delivery device of Claim 4 wherein the peel strength of the device is at least about 40 percent less than the bond strength between the barrier layer and the foam layer.

8. The drug delivery device of Claim 5 wherein the peel strength of the device is at least about 20 percent less than the bond strength between the barrier layer and the foam layer.

9. The drug delivery device of Claim 5 wherein the peel strength of the device is at least about 40 percent less than the bond strength between the barrier layer and the foam layer.

10. The drug delivery device of Claim 1 wherein the barrier layer is nonadhesively bonded to the foam layer.

11. The drug delivery device of Claim 5 wherein the barrier layer is flame bonded or vacuum laminated to the foam layer.

12. The drug delivery device of Claim 1 wherein the drug is a topical analgesic selected from the group consisting of menthol, methyl salicylate, camphor capsaicin and their mixtures.

13. The drug delivery device of Claim 1 wherein the drug is hydrocortisone.

14. The drug delivery device of Claim 1 configured as a facial mask.

15. The drug delivery device of Claim 14 wherein the mask is a single unit.

16. The drug delivery device of Claim 14 wherein the mask is a plurality of individual units of different configuration.

17. The drug delivery device of Claim 14 wherein the drug is a dermatologically and/or cosmetically beneficial active agent.

18. A process for manufacturing a nonocclusive drug delivery device which comprises:
a) bonding a substantially moisture vapor permeable, liquid impermeable. flexible thermoplastic barrier layer to the upper surface of an open cell, flexible, oleophilic thermoplastic foam layer possessing predetermined adhesive and drug depot zones separated from one another by a predetermined drug migration barrier zone;
b) applying a first release liner possessing an opening and having a layer or contact adhesive upon its lower surface to the lower surface of the foam layer with the adhesive contacting and infiltrating the adhesive zone of the foam layer, the opening in the release liner exposing a portion of the lower surface of the foam layer including the drug depot zone and drug migration barrier zone;
c) introducing a predetermined quantity of drug composition comprising a drug and an oleophilic drug delivery vehicle into the exposed drug depot zone;
d) removing the first release liner to expose the entire lower surface of the foam layer, the contact adhesive remaining within the adhesive zone of the foam layer; and, e) applying a second release liner to the lower surface of the foam layer to fully seal said surface, wherein bond strength between the barrier layer and foam layer resist separation of the barrier layer from the foam layer when the drug delivery device is subjected to the flexing and/or stretching forces normally encountered during its useful applied life.

19. The process of Claim 18 wherein the barrier layer is nonadhesively bonded to the foam layer.

20. The process of Claim 19 wherein the barrier layer is flame bonded or vacuum bonded to the foam layer.