CA1144027A - Therapeutic system for administering drugs to the skin - Google Patents
Therapeutic system for administering drugs to the skinInfo
- Publication number
- CA1144027A CA1144027A CA000369935A CA369935A CA1144027A CA 1144027 A CA1144027 A CA 1144027A CA 000369935 A CA000369935 A CA 000369935A CA 369935 A CA369935 A CA 369935A CA 1144027 A CA1144027 A CA 1144027A
- Authority
- CA
- Canada
- Prior art keywords
- drug
- che
- contact adhesive
- carrier
- bandage
- Prior art date
- 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.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/00051—Accessories for dressings
- A61F13/00063—Accessories for dressings comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/02—Adhesive plasters or dressings
- A61F13/0246—Adhesive plasters or dressings characterised by the skin adhering layer
- A61F13/0256—Adhesive plasters or dressings characterised by the skin adhering layer characterized by the parametric properties of the adhesive
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/15—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators
- A61F13/84—Accessories, not otherwise provided for, for absorbent pads
- A61F13/8405—Additives, e.g. for odour, disinfectant or pH control
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F2013/00361—Plasters
- A61F2013/00902—Plasters containing means
- A61F2013/00906—Plasters containing means for transcutaneous or transdermal drugs application
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/15—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators
- A61F13/51—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the outer layers
- A61F13/514—Backsheet, i.e. the impermeable cover or layer furthest from the skin
- A61F13/51401—Backsheet, i.e. the impermeable cover or layer furthest from the skin characterised by the material
- A61F2013/51409—Backsheet, i.e. the impermeable cover or layer furthest from the skin characterised by the material being a film
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
Abstract
THERAPEUTIC SYSTEM FOR ADMINISTERING
DRUGS TO THE SKIN
Abstract A bandage for administering drugs to the skin that consists of an impermeable backing layer, a drug reservoir layer composed of drug and a carrier, and a contact adhesive layer by which the bandage is adhered to the skin. The contact adhesive layer controls the rate at which drug is administered and maintains that rate at an approximately constant level by virture of there being a particular correleation between the solubility of the drug in the carrier and in the contact adhesive, the diffusion coefficient of the drug in the carrier and in the contact adhesive, the concentration of drug in the reservoir, and the thickness of the contact adhesive layer.
DRUGS TO THE SKIN
Abstract A bandage for administering drugs to the skin that consists of an impermeable backing layer, a drug reservoir layer composed of drug and a carrier, and a contact adhesive layer by which the bandage is adhered to the skin. The contact adhesive layer controls the rate at which drug is administered and maintains that rate at an approximately constant level by virture of there being a particular correleation between the solubility of the drug in the carrier and in the contact adhesive, the diffusion coefficient of the drug in the carrier and in the contact adhesive, the concentration of drug in the reservoir, and the thickness of the contact adhesive layer.
Description
2~
T~ERAPEUTiC SYSTEM FOR ADMINISTE~ING
DRUGS TO THE SKIN
~echnical Fi~ld This invention relates to therapeutic sys~ems in the Lorm or bandages rbac admini,cer drugs co che skin at an approximately constant ra~e ove~ a substantial portion OL
che administracion period.
Description of the Prior Art 3andages cha~ administer drugs ;o the skin or mucosa bave been known for some eime. U.S. 3,249,109 describes a ~wo layer topical dressing that consists of an adhesive l; base layer made of hydrated gelatin and drug, and a fabric bac~ing layer. Such bandages eypically release drug at either an unpredictable or inconstan~ rate.
In the early 1970s patents relating to bandages thae release drug at a substancially constant race began to appear. U.S. 3,5~8,122 describes a multilayer bandage comprising a backing layer, a drug reservoir layer, and a contact ad~esive layer by wbicb che bandage is stuck to ehe skin or muco~a. The drug ~eservoir may consist of a core of ei~her neat trug or drug mixed with a drug permeable carrier and a wall that surrounds the core ant is made OL-~; a drug release rate concrolling material. The rate of drug release depend on che rate at w~ich drug tiffusas chrougb che wall. U.S. 3,797,494 describes another ty~e of su~staneially con eane release bandage. The '494 bandage i, a andwich-cype 1 amina~2 having a backing layer, a drug reservoir layer made from a drug-carrier mix~ure, a drug rel ase rate e3ntrolling micropo~ous membrane layer, ant a concacc adhesive layer. The race or drug release from ;be '494 bantage depends on che raee ar which drug tiffuses chrougb the microporous membrane.
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In the ba~dages of both 'lZ2 and '494 tne contact ad'nesive layer plays a passive, insignificant role wic~ respec~ to drug release race; that i5, the drug that passes through che wall/membrane migrates quickly t~rough t~e contact adhesive layer to ehe skin. Co~pared to the simple two S layer bandage oE the '109 pacent ~bese subscantially constant release bandages function well. They are, however, more complex and hence cosclier t~an the more simple bandages.
lQ Discloqure of the Inven~ion Tbe invention resides in che discovery cbat an approxima~ely constant release of drug may be achieved from a bandage that is a relatively simple laminace of a la backing layer, a drug reservoir layer, and a contac~
adhesive layer and which does ~Ot involve the drug release rate controlling waIl or microporous membrane of the above-tescribed patents. T~is unexpected achievemenc rests on ehere being a par~icular correlation beeween the solubility of c~e drug in che contact adhesive composition and in che carrier of the drug reserv~ir, tbe diffusion coefficient of tbe drug in the coneact adhesive composition and in the carrier of tbe drug reservoir, the concentracion of drug in ehe drug reservoir, and the tbickness of the coneact adhesive layer.
Speciically, the inven~ion is a ther~peutic system, in t~e form of a bandage, ~or admir.iseering a drug co che skin ror a predeeer~ined time period comprising:
(a) a backing lamina ~at is substan~ially imper-meable ~o che trug, one face or' whic~ ~orms Che cop of che ba~dage;
(b) a drug reservoi, lamina adjacene ~he opposite .ace of ehe backing la~ina comprising che drug dispersed in a carrier that is permea~le ~o the drug; and ;
T~ERAPEUTiC SYSTEM FOR ADMINISTE~ING
DRUGS TO THE SKIN
~echnical Fi~ld This invention relates to therapeutic sys~ems in the Lorm or bandages rbac admini,cer drugs co che skin at an approximately constant ra~e ove~ a substantial portion OL
che administracion period.
Description of the Prior Art 3andages cha~ administer drugs ;o the skin or mucosa bave been known for some eime. U.S. 3,249,109 describes a ~wo layer topical dressing that consists of an adhesive l; base layer made of hydrated gelatin and drug, and a fabric bac~ing layer. Such bandages eypically release drug at either an unpredictable or inconstan~ rate.
In the early 1970s patents relating to bandages thae release drug at a substancially constant race began to appear. U.S. 3,5~8,122 describes a multilayer bandage comprising a backing layer, a drug reservoir layer, and a contact ad~esive layer by wbicb che bandage is stuck to ehe skin or muco~a. The drug ~eservoir may consist of a core of ei~her neat trug or drug mixed with a drug permeable carrier and a wall that surrounds the core ant is made OL-~; a drug release rate concrolling material. The rate of drug release depend on che rate at w~ich drug tiffusas chrougb che wall. U.S. 3,797,494 describes another ty~e of su~staneially con eane release bandage. The '494 bandage i, a andwich-cype 1 amina~2 having a backing layer, a drug reservoir layer made from a drug-carrier mix~ure, a drug rel ase rate e3ntrolling micropo~ous membrane layer, ant a concacc adhesive layer. The race or drug release from ;be '494 bantage depends on che raee ar which drug tiffuses chrougb the microporous membrane.
,. , ~
, ~ ~
, ~ .
-2~
In the ba~dages of both 'lZ2 and '494 tne contact ad'nesive layer plays a passive, insignificant role wic~ respec~ to drug release race; that i5, the drug that passes through che wall/membrane migrates quickly t~rough t~e contact adhesive layer to ehe skin. Co~pared to the simple two S layer bandage oE the '109 pacent ~bese subscantially constant release bandages function well. They are, however, more complex and hence cosclier t~an the more simple bandages.
lQ Discloqure of the Inven~ion Tbe invention resides in che discovery cbat an approxima~ely constant release of drug may be achieved from a bandage that is a relatively simple laminace of a la backing layer, a drug reservoir layer, and a contac~
adhesive layer and which does ~Ot involve the drug release rate controlling waIl or microporous membrane of the above-tescribed patents. T~is unexpected achievemenc rests on ehere being a par~icular correlation beeween the solubility of c~e drug in che contact adhesive composition and in che carrier of the drug reserv~ir, tbe diffusion coefficient of tbe drug in the coneact adhesive composition and in the carrier of tbe drug reservoir, the concentracion of drug in ehe drug reservoir, and the tbickness of the coneact adhesive layer.
Speciically, the inven~ion is a ther~peutic system, in t~e form of a bandage, ~or admir.iseering a drug co che skin ror a predeeer~ined time period comprising:
(a) a backing lamina ~at is substan~ially imper-meable ~o che trug, one face or' whic~ ~orms Che cop of che ba~dage;
(b) a drug reservoi, lamina adjacene ~he opposite .ace of ehe backing la~ina comprising che drug dispersed in a carrier that is permea~le ~o the drug; and ;
3;
3~ 4~2~
. -~c) a contact adhesive lamina adjacent and below the drug reservoi~ lamina comprising a contact adhesive composition that is permeable to the trug, characterized in that the following condieions are mee over a substantial portion . 5 of said time per iod (i~ .he conceneration of the drug in the contace adheslve lamina, CcA mg/cm3, is not greaeer than the solubility of the dru~ in the contact adhesive composition, CScA m~lcm3, and (ii) ths raCio ~CA ' CSCA
. ~ l2 CA ~ ~ t :. 15 is in the range of about O.Ol and about 0.7, w~erein DCA is the diE~usion coefficient of che drug in the coneact adhesive composition in cm2/hr, ~CA is ehe chickness of tbe contacc adhesive lamina in cm, DDR is the diffusion coefficienc of che drug in che carrier in cm2/hr, C~R is the eoncentration of ~rug in che drug reservoir in ~g/cm3, .~ Cs3R is the solubiliey of the drug in: the carrier in 25~ mg/c~3, and t is any time during sait ~ime ~pe.iod in hr.
The ter~ "substantial" as applied ~o said time:period is ~' intended to mean at least 50b. Typically the condicions . will prevail over at least 75% of:che ti~e periot. Ihe - 30 maintena~ce of ~uch condi~io~s will typicalIy result in the release race declining less than 30Z over the eime period.
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~ri~. D~sc,$ocion or ehe ~.awi~s In che.drawings:
Figure 1, which is not co scale, is a seccional view of ~be inve~cion bandag~;
Figur~ 2 is a g-ap~ o~ scopolamine re1eas2 ~a;e ve~sus time for che ba~aOs o~ Examo13 1 and cne componencs ;hereof;
a~d Figure 3 is a g~aph or nic-oglycer n release ;ac3 versus cime ror che bandages of ExamDles 2 and 3.
Descriocion of c~bodi;~enes o~ che Invention Figure 1 illus~races che basic scruc~urs of ehe ~andage, : I; generally tesigna~ed 10, before ic is applied co the skiQ. The componen~s of ~anda8a 10 ar~, ~rom che cop: a~ impermeable backing layer 11, a drug reservoi- layer 12 co~posed of a drug :: 13 dispersed in a carrier 14, a coneact athesive layer 15, nd ~: an i~per~e~ble s~rippa~le coacing or release liner layer 15.
~0 Layer 16 is removed to expose layar 15 beore che bantage is appliet co che skin. Depending on ehe pareicular drYg, carrier, and adhesive composicion involved it ~ay be necessary or desi~able eo enclose the sides of ~e bandage 10 wich an i~p~meabte coaeing or other~ise seal ehe sites co ?re~e~t drug, carrier, ant/or adhesive fro~ evaporating, bleedi~g, exudi~g, leaking or o~her~ise exici~g rrom che ba~dage via ics sides.
Bac~i~g layer 11 prevencs dru~ fro~ being ~eleas~d via che cop surface o~ reserv~ir I~yer 12. I; also ~erves 2S 2 proteccive lay~r ~r coYer ~or the bandage wbe~ ic is i~ place 3C on che ski~ or ~ucosa. As suc~ usc be i~pe~3eable to the - tzug, waeer, a~d che carrier. Macarials ror ~ak1ng such ~acking ~emb~rs er3 disclosed in che arr, for ins;2nce i~ U,S.
Pacenc No. 3,;g8,122 ac coluGn 5, lines 56 to 7L
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Drug re~ervoi~ 12 is composed o- a mix.ure o. a c~r-ie~
and che dru~. In ~osc instanc s t~e d;ug w-ll iniclally ~e presene ~r~a~lv in eXC355 of ics solubilicy in ~he carrIer ~a~erial. ~hus, che trug is present in cbe ~eservoir in boc.
dissolved and undissolved rorm. Th~ d.ug concene of che rese~voir sboult be kepe below cb2 conc~ncracion ac ~ ch .;a~
carrier ce~ses co be a concinuous ?hase and there is sign~flc2nt particle-co-parcicl~ concac~ becween disp~r,ed dru~ pa.ticl~s.
: Typically ehe ~axi3um drug conc~nc e~ac can be achi~ved wich~uc tO encouncering such conticions is about 357~ drug by volume i~ cne ,eservoir. As indic~cQd previously, c~e carrier is perme2ble co cbe ~rug. In chis regard, the solubility o~ the drug in ~he carrier will usually be in che range o~ 2DOUt 0.1 mg/cm3 ~o about lOO ~g/c~3 ant che diffusion coefficie~c of drug in l~ che carrier will ~ormally be in the range of aboue 1 x 10-eo about l x 10-7 c~2/seC. Pr~ferably the drug reservoir mixture is in che form of a cobesive semisolid, suc;~ as a ~hac adheres scrongly to the bac~ing layer and concac~ adhesiv~
layer . Otherwis~, me ns for eonfining tbe ~eservoir and provid-ing struccural inceg~icy for che sys~e~ ~usc be included.
Exa~pl~s or such means are side walls, overlays, and edge sealing. The particular carrier to be used wiLl depe~d in large par~ ~pon t~ pa~ticu~ar drug involvet. Silicone-based : carriers and car~iers made from ~ixrures of ~ineral oil a~d ~ 25 polyisoburenes ma~ be used wi th many drugs. Th~ pacencs reer.ed :: co in the Desc~ipeion Ot Prio~ Are a~ove diselose example~ of ochcr carri~rs cha~ r~tay be used.
rhe concace adhesive Lay~r }5 plays cbe princl?a' .ole in.
co~~olling the ra~e a~ wbicn drug is .el~ ed ~rom bandage lO
k , too, is pe~eabl~ co ~be drug. ~he solubili.y ~f ebe drug 3~ i~ the co~pasicio~ ro~ w~ich ~he lay~ is made will nor~all~
~e i~ che same range 2S for c~e carrie~ nam~ly 0.1 ;o lOO
mg/c~3. Li~ewis~ ~he diffusion coe~lci~r or che ~;u~ in cbe concac~ adhesive c3~p~sicion will usually be in ch~ ~an~e of 1 x 10-11 to 1 x 10-7 c~2/sec. As indic~ted above, che concen~racion of trug 1~ the concacc adhesive layer is l~ss , .
, .
- :.
-6- ~4~27 e~an che solubllity of the drug i~ ~he c~nt2ce adhesi~t~ com-posicion over at leas~ a substantial portion or cne ei~e ?e~iod over which che drug is to be adminis~red. I.' ~o drug is incorporaced in~o che con~act adhesive layer before ehe ba~dage is aecached eo ehe skin, t~ac condition wiLl ?revail over tbe e~tire cime period. 0~ c;~e o~her ~a~t, if d-ug is incorporat_d inco ebe contacc adhesive befor-hand so chac che actual concenzracion exceeds the solubility, chac condicion will prevail o~ly afe r an initi~l poreion o~ che ci~e Deriod during w~ich the d. ug is de?leced from excess down co sa~uracion and below. Such i~corporacion o~ drug ineo ~he layer beforehand is ~ade i~ i~ is ~ecessary or tesirable co ad iniscer 2n i~.tial surge or pulse o~ drug. ~owever, as indicaced the duracio~ of ehis surge or pulse will be short relative ;o tbe coC2l admi~is-eracion p~riod.
Depending on ~he trug involved and che desired c ime period over w~ich ehe drug is to be ad~i~iscered, ic m2y be possible to s~ploy the sa~e maeerial as boc~ che carrier and the coneact adhesive comp~sicion. When ebis ic done, DCA and D~R will be equal and CScA and C5DR wiil be equal and che above rario may be simplified. Under suc~ circu~s~a~ces, ~CA
and C~R become che parameeers t~ac ~ay b~ varied to ~ake a ~andage ~hac conforms co the inv~ncion. In ch.is regart, the msxi~um C~R thae can be employed is tescribed abo~e. While ther~ is no cheorecical ~ini~u~ or ~axi~um for ~CA~ t~is paramete~ will, ~or prac~ical purposes usually be in ~hs r2nge o ;0 mic~ons co 2 mm.
c;ne invention ban~ages c~e -aeio -:.
D~A CSCA
~0 . ~CA ~ D~ CD~ I~DR~ 1/2 .~ i3 in ehe range o~ abou~ O.Ql and abou; 0.7 over a subscanci21 por~ion ~t ;he cime peri~d during which the drug is adm~nisc~red.
3; Pref~raoly i~ will ~e maincai~ed over c~.e enci.~ period. Ia : . ~
i~ . ,........ . _ . . .. .
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this r gard, for mosc cberapies c'ne adminiseracion period (pec bandage) will be i~ ehe -ange or 2'. hr a~d one ~ee~.
Th~ rollowi~g examoles further illusc~ac~ the invencion, T~ey ar~ QOc i~cended co limic c~e inven~ion in any way.
Unless indicaced otherwise pro~or~ions are bv weighc.
Examole 1 A. A banG28e for adminisrering sco w lamine tra~sdermally ro~ approxi~ately 72 ~r, such as mig'at be used co inhi~ic nausea or ver~lgo, was ate as follows. A solution o~ 1.5 parcs bigh ~olecular w~ight polyisobucene (l?200,00~ viscoslcy average molecular weighe), 1.9 pares low ~olecula~ wei_hc polyisobutene (35,000 viseosity average molecular weighc), 3.0 pares ~ineral oi~ (10 ;p ac 2SC), 0.8 parts scopolamine, a~d 41 pa~ts chloroform was solvene casc onco a 0.07 mm chick backing rilm or alu~iniz~d polyeâcer. Tbe resuking Laye~ o. ~olyisobutene, ~ineral oil, and scopolamine was 0.04 mm ~bic~. ~hac lay~r conscicuced che drug ~eservoir o~ the bandage, wich D~
being 2 x 10-8 c~2/sec, CSDR being 1 mg/cm3. and CDR being 133.1 ~8ic~3. The same mixture of ~i~eral oil and high and low ~olecular ~ig~t polyisobucanes was blended wich 0.13 parts o~ scopolam~ne and che blend was solvenc cast onto a Q.08 ~ thic~ scrippabl~ coaeing Layer ~ade o~ siliconized ~olv~seer The ~esulcing solvenc case layer was 85.3 microns thic~ (XCA).
k eons~i~uted ;he eoncac~ adhes,ve layer or the bandag~, wich OCA '~eing ~ x~ 10-a c~ c, CSD~:beinæ 1 mg/c~3, and CcA
bei:ng:21.82 ~/cm3. The ~wo la~1~aces were chen lAminacsd ~: cog~cher wlcb ehe ~rug res-Fvoir facing cne coneact adh~sive.
. 3 ~. In vit~5 releas~ ~ace C25CS using:sca~dard cQchniques 4r~ were carr~ed:out on ~he bandage tescri~ed i.. A above. For comparis~n purposes iden.ical cescs we~e ca ri~d out on c~e d.ug ~eservoi~ alone and cb2 coneac~ adheçlve alone. rhe resulcs o~
ehese cescs are reDsr-ed graphically i~ Figure 2.
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8 ~ 7 CcA was equal eo or less ehan CScA -7fce- about 10 hr.
The above 2encioned ra;io ranged between abou~ 0.4 2~1~i about 0. ï over ehe ~e~iod c D 24 hr ~o t ~ 72 'nr .
As depicted in Figure 2 during che 'irsc 1~ hr che ba~dage rel~ased scopolamine a; relacively h~gh ~-ces. T~is was caused primarily by ~he inicial inclusion a sco~l ~ir.e i~
che con~acc adbesive (CcA a~ c ~ O was about 22 ei~es Csc~).
~here~fter the release rate leveled off ac abouc 4-6 mcg/c~2 ;~7.
The comoarison tes~s on che d~u~ reservoi~ alone and che conract adhesive alone clearly show chac che r~lease ~ace sf tbe enci~e bandage is noc reiaced ;o tbe sum of ~he ~elease races chat occur :~o~ cbe compcnencs taken by tbemselves. ~ote especially ~bat after abou~ 1 day the co~cace adhesive was exbausced of scopola~ine and afeer aboue 1 l/2 days ebe drug eservoir ~as depleeed af scop~La~ine.
Exa=~le 2 A. A banda~e ror ad~i~isceri~g ~i;roglycerin ;rans-dermally ~or app~cxi~acely 24 ~r, sucb as ~ig~r be used co treae angina, was ~ade as follows. A blend of 67 pa~ts silic~e fluid (100,00~ c~) and 33 parts of nitroglycerin on lactose (1~10 by wei~ht) ~as cas~ onco a 0.07 mm ~hick backing fi~ of 21u~i~ized polyescer. Th~ resulei~g la~e~ or thac ble~d was 0.25 mm chic~ a~d ic cons~icu~ed che d~ug -eservoir of ehe bzntage, wicb D~R bein~ 4 x 10-6 c~2/sec, C~ beir.g 33 mg/c~3, ant CS~R being 2 2g/c~3. A s~lu~icn or ecbyle~e/
vi~yLaceca~e copoly2er (9% vi2ylacecac~ mec~yle~e cbloride W2S, soive~c casc onco a 0.û8 3~ chick scripQable coacir.g layer made o~ silico~ized po~yester. T~e r~sulcirlg ~ay~r or copol~Jmer was ].OO
~ic~ons thi~ls (,~CA) and cons~icuted th~ coneace adhesive laye~ o~ the bandage, wich 13~ A bei;~g 7 x 10-~ c;~2/sec ar~d CScA bein~; 5 ag/c:~3. Tbe ~wo lal;Linaces were t~n la~inated toge~er wi~n the drug .ese~oir facing ;he concac~
adhes i ve .
, ~, :' . , , _9~
3. In viero release race cests usin~ scanda d terhn.~u~s we~e carried ou~ on che bandage of A above. The reculcs or ~hose tests are reported graphically i3 Figu.e 3 wi;h che da~a points b~ing designaced by triangles. The above ~encioned raeio ranged beeween abo~l~ 0.03 and 0.08 over tbe period c - 3 co t ~ 30 hr. As sbown, che ralsas2 race or drug tecli~ed slighcly over ebe period but ore closelv approxi~a~d zero order release chan rirje order .elsase.
Examole 3 A. For cofflparison purposes a bandage fo. admi~istering aic~o~lycerin transdermally ror approxi3ately 24 hr was ~ade tbat did Qoe ~eet the criceria c~ ch~ inven~ian. ~he compa~ison bandage was made as i~ Exa~ple 2 exceoc chat che carrier or che drug reservoir was petrola~u~ US~ racher chan silicone fluit, ant ~he contace a~hesive Layer was ljO ~icrons chic~ and was ~ade of an ethylene/ vi~ylacecace copolymer coneaining }8%
vinylacerace. C~R was 20 ~glc~3~ CS~ was 1.2 ~glcm3, arld D~R was ~ x 10-5 c~2/sec.
B. In vitro r~lease rate cescs on ehe bandage of A
wer~ carried oue as in Exa~ple 2. The results or ehese ces~s are ai~o repa~c2d i~ Figure 3, with che daca points being repre~e~d by squares. Th~ ;above mencioned ~acio rang~d b~cween abaut 5 . 8 a~ad 17 over t~le period c ~ 3 co ; ~ 30 b. .
As showrl, rel~ase r c~ dsclined dr2s;ical.1~ relacive co che ~andage or cxa~pLe 2, wirh re~lease rac~ closely aporoxi:~a;ing .irs; order r~leas~.
Moti~icaeio~s of ehe a~v~ t~se~ibed bandage cn2c are obv~ous co cho~e o~ sklll in the ?har3~c~utic21 a.t arQ intend~d eo be wichi~ cne 5cope of che following claims.
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. -~c) a contact adhesive lamina adjacent and below the drug reservoi~ lamina comprising a contact adhesive composition that is permeable to the trug, characterized in that the following condieions are mee over a substantial portion . 5 of said time per iod (i~ .he conceneration of the drug in the contace adheslve lamina, CcA mg/cm3, is not greaeer than the solubility of the dru~ in the contact adhesive composition, CScA m~lcm3, and (ii) ths raCio ~CA ' CSCA
. ~ l2 CA ~ ~ t :. 15 is in the range of about O.Ol and about 0.7, w~erein DCA is the diE~usion coefficient of che drug in the coneact adhesive composition in cm2/hr, ~CA is ehe chickness of tbe contacc adhesive lamina in cm, DDR is the diffusion coefficienc of che drug in che carrier in cm2/hr, C~R is the eoncentration of ~rug in che drug reservoir in ~g/cm3, .~ Cs3R is the solubiliey of the drug in: the carrier in 25~ mg/c~3, and t is any time during sait ~ime ~pe.iod in hr.
The ter~ "substantial" as applied ~o said time:period is ~' intended to mean at least 50b. Typically the condicions . will prevail over at least 75% of:che ti~e periot. Ihe - 30 maintena~ce of ~uch condi~io~s will typicalIy result in the release race declining less than 30Z over the eime period.
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~ri~. D~sc,$ocion or ehe ~.awi~s In che.drawings:
Figure 1, which is not co scale, is a seccional view of ~be inve~cion bandag~;
Figur~ 2 is a g-ap~ o~ scopolamine re1eas2 ~a;e ve~sus time for che ba~aOs o~ Examo13 1 and cne componencs ;hereof;
a~d Figure 3 is a g~aph or nic-oglycer n release ;ac3 versus cime ror che bandages of ExamDles 2 and 3.
Descriocion of c~bodi;~enes o~ che Invention Figure 1 illus~races che basic scruc~urs of ehe ~andage, : I; generally tesigna~ed 10, before ic is applied co the skiQ. The componen~s of ~anda8a 10 ar~, ~rom che cop: a~ impermeable backing layer 11, a drug reservoi- layer 12 co~posed of a drug :: 13 dispersed in a carrier 14, a coneact athesive layer 15, nd ~: an i~per~e~ble s~rippa~le coacing or release liner layer 15.
~0 Layer 16 is removed to expose layar 15 beore che bantage is appliet co che skin. Depending on ehe pareicular drYg, carrier, and adhesive composicion involved it ~ay be necessary or desi~able eo enclose the sides of ~e bandage 10 wich an i~p~meabte coaeing or other~ise seal ehe sites co ?re~e~t drug, carrier, ant/or adhesive fro~ evaporating, bleedi~g, exudi~g, leaking or o~her~ise exici~g rrom che ba~dage via ics sides.
Bac~i~g layer 11 prevencs dru~ fro~ being ~eleas~d via che cop surface o~ reserv~ir I~yer 12. I; also ~erves 2S 2 proteccive lay~r ~r coYer ~or the bandage wbe~ ic is i~ place 3C on che ski~ or ~ucosa. As suc~ usc be i~pe~3eable to the - tzug, waeer, a~d che carrier. Macarials ror ~ak1ng such ~acking ~emb~rs er3 disclosed in che arr, for ins;2nce i~ U,S.
Pacenc No. 3,;g8,122 ac coluGn 5, lines 56 to 7L
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Drug re~ervoi~ 12 is composed o- a mix.ure o. a c~r-ie~
and che dru~. In ~osc instanc s t~e d;ug w-ll iniclally ~e presene ~r~a~lv in eXC355 of ics solubilicy in ~he carrIer ~a~erial. ~hus, che trug is present in cbe ~eservoir in boc.
dissolved and undissolved rorm. Th~ d.ug concene of che rese~voir sboult be kepe below cb2 conc~ncracion ac ~ ch .;a~
carrier ce~ses co be a concinuous ?hase and there is sign~flc2nt particle-co-parcicl~ concac~ becween disp~r,ed dru~ pa.ticl~s.
: Typically ehe ~axi3um drug conc~nc e~ac can be achi~ved wich~uc tO encouncering such conticions is about 357~ drug by volume i~ cne ,eservoir. As indic~cQd previously, c~e carrier is perme2ble co cbe ~rug. In chis regard, the solubility o~ the drug in ~he carrier will usually be in che range o~ 2DOUt 0.1 mg/cm3 ~o about lOO ~g/c~3 ant che diffusion coefficie~c of drug in l~ che carrier will ~ormally be in the range of aboue 1 x 10-eo about l x 10-7 c~2/seC. Pr~ferably the drug reservoir mixture is in che form of a cobesive semisolid, suc;~ as a ~hac adheres scrongly to the bac~ing layer and concac~ adhesiv~
layer . Otherwis~, me ns for eonfining tbe ~eservoir and provid-ing struccural inceg~icy for che sys~e~ ~usc be included.
Exa~pl~s or such means are side walls, overlays, and edge sealing. The particular carrier to be used wiLl depe~d in large par~ ~pon t~ pa~ticu~ar drug involvet. Silicone-based : carriers and car~iers made from ~ixrures of ~ineral oil a~d ~ 25 polyisoburenes ma~ be used wi th many drugs. Th~ pacencs reer.ed :: co in the Desc~ipeion Ot Prio~ Are a~ove diselose example~ of ochcr carri~rs cha~ r~tay be used.
rhe concace adhesive Lay~r }5 plays cbe princl?a' .ole in.
co~~olling the ra~e a~ wbicn drug is .el~ ed ~rom bandage lO
k , too, is pe~eabl~ co ~be drug. ~he solubili.y ~f ebe drug 3~ i~ the co~pasicio~ ro~ w~ich ~he lay~ is made will nor~all~
~e i~ che same range 2S for c~e carrie~ nam~ly 0.1 ;o lOO
mg/c~3. Li~ewis~ ~he diffusion coe~lci~r or che ~;u~ in cbe concac~ adhesive c3~p~sicion will usually be in ch~ ~an~e of 1 x 10-11 to 1 x 10-7 c~2/sec. As indic~ted above, che concen~racion of trug 1~ the concacc adhesive layer is l~ss , .
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-6- ~4~27 e~an che solubllity of the drug i~ ~he c~nt2ce adhesi~t~ com-posicion over at leas~ a substantial portion or cne ei~e ?e~iod over which che drug is to be adminis~red. I.' ~o drug is incorporaced in~o che con~act adhesive layer before ehe ba~dage is aecached eo ehe skin, t~ac condition wiLl ?revail over tbe e~tire cime period. 0~ c;~e o~her ~a~t, if d-ug is incorporat_d inco ebe contacc adhesive befor-hand so chac che actual concenzracion exceeds the solubility, chac condicion will prevail o~ly afe r an initi~l poreion o~ che ci~e Deriod during w~ich the d. ug is de?leced from excess down co sa~uracion and below. Such i~corporacion o~ drug ineo ~he layer beforehand is ~ade i~ i~ is ~ecessary or tesirable co ad iniscer 2n i~.tial surge or pulse o~ drug. ~owever, as indicaced the duracio~ of ehis surge or pulse will be short relative ;o tbe coC2l admi~is-eracion p~riod.
Depending on ~he trug involved and che desired c ime period over w~ich ehe drug is to be ad~i~iscered, ic m2y be possible to s~ploy the sa~e maeerial as boc~ che carrier and the coneact adhesive comp~sicion. When ebis ic done, DCA and D~R will be equal and CScA and C5DR wiil be equal and che above rario may be simplified. Under suc~ circu~s~a~ces, ~CA
and C~R become che parameeers t~ac ~ay b~ varied to ~ake a ~andage ~hac conforms co the inv~ncion. In ch.is regart, the msxi~um C~R thae can be employed is tescribed abo~e. While ther~ is no cheorecical ~ini~u~ or ~axi~um for ~CA~ t~is paramete~ will, ~or prac~ical purposes usually be in ~hs r2nge o ;0 mic~ons co 2 mm.
c;ne invention ban~ages c~e -aeio -:.
D~A CSCA
~0 . ~CA ~ D~ CD~ I~DR~ 1/2 .~ i3 in ehe range o~ abou~ O.Ql and abou; 0.7 over a subscanci21 por~ion ~t ;he cime peri~d during which the drug is adm~nisc~red.
3; Pref~raoly i~ will ~e maincai~ed over c~.e enci.~ period. Ia : . ~
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this r gard, for mosc cberapies c'ne adminiseracion period (pec bandage) will be i~ ehe -ange or 2'. hr a~d one ~ee~.
Th~ rollowi~g examoles further illusc~ac~ the invencion, T~ey ar~ QOc i~cended co limic c~e inven~ion in any way.
Unless indicaced otherwise pro~or~ions are bv weighc.
Examole 1 A. A banG28e for adminisrering sco w lamine tra~sdermally ro~ approxi~ately 72 ~r, such as mig'at be used co inhi~ic nausea or ver~lgo, was ate as follows. A solution o~ 1.5 parcs bigh ~olecular w~ight polyisobucene (l?200,00~ viscoslcy average molecular weighe), 1.9 pares low ~olecula~ wei_hc polyisobutene (35,000 viseosity average molecular weighc), 3.0 pares ~ineral oi~ (10 ;p ac 2SC), 0.8 parts scopolamine, a~d 41 pa~ts chloroform was solvene casc onco a 0.07 mm chick backing rilm or alu~iniz~d polyeâcer. Tbe resuking Laye~ o. ~olyisobutene, ~ineral oil, and scopolamine was 0.04 mm ~bic~. ~hac lay~r conscicuced che drug ~eservoir o~ the bandage, wich D~
being 2 x 10-8 c~2/sec, CSDR being 1 mg/cm3. and CDR being 133.1 ~8ic~3. The same mixture of ~i~eral oil and high and low ~olecular ~ig~t polyisobucanes was blended wich 0.13 parts o~ scopolam~ne and che blend was solvenc cast onto a Q.08 ~ thic~ scrippabl~ coaeing Layer ~ade o~ siliconized ~olv~seer The ~esulcing solvenc case layer was 85.3 microns thic~ (XCA).
k eons~i~uted ;he eoncac~ adhes,ve layer or the bandag~, wich OCA '~eing ~ x~ 10-a c~ c, CSD~:beinæ 1 mg/c~3, and CcA
bei:ng:21.82 ~/cm3. The ~wo la~1~aces were chen lAminacsd ~: cog~cher wlcb ehe ~rug res-Fvoir facing cne coneact adh~sive.
. 3 ~. In vit~5 releas~ ~ace C25CS using:sca~dard cQchniques 4r~ were carr~ed:out on ~he bandage tescri~ed i.. A above. For comparis~n purposes iden.ical cescs we~e ca ri~d out on c~e d.ug ~eservoi~ alone and cb2 coneac~ adheçlve alone. rhe resulcs o~
ehese cescs are reDsr-ed graphically i~ Figure 2.
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8 ~ 7 CcA was equal eo or less ehan CScA -7fce- about 10 hr.
The above 2encioned ra;io ranged between abou~ 0.4 2~1~i about 0. ï over ehe ~e~iod c D 24 hr ~o t ~ 72 'nr .
As depicted in Figure 2 during che 'irsc 1~ hr che ba~dage rel~ased scopolamine a; relacively h~gh ~-ces. T~is was caused primarily by ~he inicial inclusion a sco~l ~ir.e i~
che con~acc adbesive (CcA a~ c ~ O was about 22 ei~es Csc~).
~here~fter the release rate leveled off ac abouc 4-6 mcg/c~2 ;~7.
The comoarison tes~s on che d~u~ reservoi~ alone and che conract adhesive alone clearly show chac che r~lease ~ace sf tbe enci~e bandage is noc reiaced ;o tbe sum of ~he ~elease races chat occur :~o~ cbe compcnencs taken by tbemselves. ~ote especially ~bat after abou~ 1 day the co~cace adhesive was exbausced of scopola~ine and afeer aboue 1 l/2 days ebe drug eservoir ~as depleeed af scop~La~ine.
Exa=~le 2 A. A banda~e ror ad~i~isceri~g ~i;roglycerin ;rans-dermally ~or app~cxi~acely 24 ~r, sucb as ~ig~r be used co treae angina, was ~ade as follows. A blend of 67 pa~ts silic~e fluid (100,00~ c~) and 33 parts of nitroglycerin on lactose (1~10 by wei~ht) ~as cas~ onco a 0.07 mm ~hick backing fi~ of 21u~i~ized polyescer. Th~ resulei~g la~e~ or thac ble~d was 0.25 mm chic~ a~d ic cons~icu~ed che d~ug -eservoir of ehe bzntage, wicb D~R bein~ 4 x 10-6 c~2/sec, C~ beir.g 33 mg/c~3, ant CS~R being 2 2g/c~3. A s~lu~icn or ecbyle~e/
vi~yLaceca~e copoly2er (9% vi2ylacecac~ mec~yle~e cbloride W2S, soive~c casc onco a 0.û8 3~ chick scripQable coacir.g layer made o~ silico~ized po~yester. T~e r~sulcirlg ~ay~r or copol~Jmer was ].OO
~ic~ons thi~ls (,~CA) and cons~icuted th~ coneace adhesive laye~ o~ the bandage, wich 13~ A bei;~g 7 x 10-~ c;~2/sec ar~d CScA bein~; 5 ag/c:~3. Tbe ~wo lal;Linaces were t~n la~inated toge~er wi~n the drug .ese~oir facing ;he concac~
adhes i ve .
, ~, :' . , , _9~
3. In viero release race cests usin~ scanda d terhn.~u~s we~e carried ou~ on che bandage of A above. The reculcs or ~hose tests are reported graphically i3 Figu.e 3 wi;h che da~a points b~ing designaced by triangles. The above ~encioned raeio ranged beeween abo~l~ 0.03 and 0.08 over tbe period c - 3 co t ~ 30 hr. As sbown, che ralsas2 race or drug tecli~ed slighcly over ebe period but ore closelv approxi~a~d zero order release chan rirje order .elsase.
Examole 3 A. For cofflparison purposes a bandage fo. admi~istering aic~o~lycerin transdermally ror approxi3ately 24 hr was ~ade tbat did Qoe ~eet the criceria c~ ch~ inven~ian. ~he compa~ison bandage was made as i~ Exa~ple 2 exceoc chat che carrier or che drug reservoir was petrola~u~ US~ racher chan silicone fluit, ant ~he contace a~hesive Layer was ljO ~icrons chic~ and was ~ade of an ethylene/ vi~ylacecace copolymer coneaining }8%
vinylacerace. C~R was 20 ~glc~3~ CS~ was 1.2 ~glcm3, arld D~R was ~ x 10-5 c~2/sec.
B. In vitro r~lease rate cescs on ehe bandage of A
wer~ carried oue as in Exa~ple 2. The results or ehese ces~s are ai~o repa~c2d i~ Figure 3, with che daca points being repre~e~d by squares. Th~ ;above mencioned ~acio rang~d b~cween abaut 5 . 8 a~ad 17 over t~le period c ~ 3 co ; ~ 30 b. .
As showrl, rel~ase r c~ dsclined dr2s;ical.1~ relacive co che ~andage or cxa~pLe 2, wirh re~lease rac~ closely aporoxi:~a;ing .irs; order r~leas~.
Moti~icaeio~s of ehe a~v~ t~se~ibed bandage cn2c are obv~ous co cho~e o~ sklll in the ?har3~c~utic21 a.t arQ intend~d eo be wichi~ cne 5cope of che following claims.
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Claims (2)
1. A bandage for administering a drug to the skin or mucosa for a predetermined time period, with t representing a time, in hours, in said time period, comprising a sandwich type laminate of:
(a) a backing lamina that is substantially imper-meable to the drug, one face of which forms the top of the bandage;
(b) a drug reservoir lamina adjacent the opposite face of the backing lamina comprising the drug dispersed in a carrier that is permeable to the drug, with the solubility of the drug in the carrier being CSDR mg/cm3, the diffusion coefficient of drug in the carrier being DDR cm2/hr, and the concentration of drug in the drug reservoir being CDR mg/cm3;
and (c) a contact adhesive lamina adjacent and below the drug reservoir lamina comprising a contact adhesive composi-tion that is permeable to the drug, with the thickness of the contact adhesive lamina being ?CA cm, the solubility of the drug in the contact adhesive composition being CSCA mg/cm3, the diffusion coefficient of drug in the contact adhesive composition being DCA cm2/hr, and the concentration of drug in the contact adhesive composition being CCA mg/cm3, characterized in that over at least a substantial portion of said time period (i) CCA is not greater than CSCA, and (ii) the ratio is in the range of about 0.01 to about 0.7.
(a) a backing lamina that is substantially imper-meable to the drug, one face of which forms the top of the bandage;
(b) a drug reservoir lamina adjacent the opposite face of the backing lamina comprising the drug dispersed in a carrier that is permeable to the drug, with the solubility of the drug in the carrier being CSDR mg/cm3, the diffusion coefficient of drug in the carrier being DDR cm2/hr, and the concentration of drug in the drug reservoir being CDR mg/cm3;
and (c) a contact adhesive lamina adjacent and below the drug reservoir lamina comprising a contact adhesive composi-tion that is permeable to the drug, with the thickness of the contact adhesive lamina being ?CA cm, the solubility of the drug in the contact adhesive composition being CSCA mg/cm3, the diffusion coefficient of drug in the contact adhesive composition being DCA cm2/hr, and the concentration of drug in the contact adhesive composition being CCA mg/cm3, characterized in that over at least a substantial portion of said time period (i) CCA is not greater than CSCA, and (ii) the ratio is in the range of about 0.01 to about 0.7.
2. The bandage of claim 1 further characterized in that CSDR is in the range of 0.1 and 100 mg cm3, CSCA is in the range of 0.1 and 100 mg cm3, DDR is in the range of 1 x 10-11 and 1 x 10-7 cm2/sec, DCA is in the range of 1 x 10-11 and 1 x 10-7 cm2/sec, and ?CA is in ehe range of 50 microns and 2 mm.
4:130:17 A-l 10/1/80-
4:130:17 A-l 10/1/80-
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/117,846 US4286592A (en) | 1980-02-04 | 1980-02-04 | Therapeutic system for administering drugs to the skin |
US117,846 | 1980-02-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1144027A true CA1144027A (en) | 1983-04-05 |
Family
ID=22375150
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000369935A Expired CA1144027A (en) | 1980-02-04 | 1981-02-03 | Therapeutic system for administering drugs to the skin |
Country Status (7)
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US (1) | US4286592A (en) |
EP (1) | EP0033615B1 (en) |
JP (1) | JPS6055044B2 (en) |
AT (1) | ATE5563T1 (en) |
AU (1) | AU533491B2 (en) |
CA (1) | CA1144027A (en) |
DE (1) | DE3161605D1 (en) |
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US4379454A (en) * | 1981-02-17 | 1983-04-12 | Alza Corporation | Dosage for coadministering drug and percutaneous absorption enhancer |
US4460372A (en) * | 1981-02-17 | 1984-07-17 | Alza Corporation | Percutaneous absorption enhancer dispenser for use in coadministering drug and percutaneous absorption enhancer |
JPS6059207B2 (en) * | 1981-03-13 | 1985-12-24 | 日東電工株式会社 | Manufacturing method for complex preparations |
US4834979A (en) * | 1981-06-29 | 1989-05-30 | Alza Corporation | Medical bandage for administering beneficial drug |
US4812313A (en) * | 1981-06-29 | 1989-03-14 | Alza Corporation | Method for lessening the incidence of anginal attacks |
US4954344A (en) * | 1981-06-29 | 1990-09-04 | Alza Corporation | Method for treating nocturnal angina |
US4849226A (en) * | 1981-06-29 | 1989-07-18 | Alza Corporation | Method for increasing oxygen supply by administering vasodilator |
US4725272A (en) * | 1981-06-29 | 1988-02-16 | Alza Corporation | Novel bandage for administering beneficial drug |
US4661105A (en) * | 1981-06-29 | 1987-04-28 | Alza Corporation | Medical bandage for administering vasodilator drug |
GB2105990B (en) * | 1981-08-27 | 1985-06-19 | Nitto Electric Ind Co | Adhesive skin patches |
US4460368A (en) * | 1981-10-29 | 1984-07-17 | Almedco, Inc. | Trans-dermal medication system |
US4532937A (en) * | 1982-12-28 | 1985-08-06 | Cuderm Corporation | Sebum collection and monitoring means and method |
US4681544A (en) * | 1983-01-13 | 1987-07-21 | Anthony Albert J | Oral pack retention system |
FR2542998B1 (en) * | 1983-03-24 | 1986-01-31 | Rhone Poulenc Sante | NEW TRANSDERMAL FORM OF ISOSORBIDE DINITRATE |
DE3315272C2 (en) * | 1983-04-27 | 1986-03-27 | Lohmann Gmbh & Co Kg, 5450 Neuwied | Pharmaceutical product and process for its manufacture |
US4564364A (en) * | 1983-05-26 | 1986-01-14 | Alza Corporation | Active agent dispenser |
JPS6016916A (en) * | 1983-07-08 | 1985-01-28 | Nitto Electric Ind Co Ltd | Substrate containing bioactive substance and preparation of said substrate |
DE3344691A1 (en) * | 1983-12-10 | 1985-06-20 | Bayer Ag, 5090 Leverkusen | ACTIVE GAS EXHAUST SYSTEMS |
DE3347277A1 (en) * | 1983-12-28 | 1985-07-11 | Bayer Ag, 5090 Leverkusen | ACTIVE SUBSTANCE DELIVERY SYSTEMS |
DK149601C (en) * | 1984-01-23 | 1987-02-02 | Coloplast As | PRESSURELY BANDAGE |
US4704282A (en) * | 1984-06-29 | 1987-11-03 | Alza Corporation | Transdermal therapeutic system having improved delivery characteristics |
US4725439A (en) * | 1984-06-29 | 1988-02-16 | Alza Corporation | Transdermal drug delivery device |
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US4237888A (en) * | 1979-03-23 | 1980-12-09 | The Upjohn Company | Two-membrane medicated device for rate-controlled administration of prostaglandins |
DE2920500A1 (en) * | 1979-05-21 | 1980-11-27 | Boehringer Sohn Ingelheim | PHARMACEUTICAL PREPARATION IN THE FORM OF A POLYACRYLATE FILM |
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- 1980-02-04 US US06/117,846 patent/US4286592A/en not_active Expired - Lifetime
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1981
- 1981-01-22 EP EP81300286A patent/EP0033615B1/en not_active Expired
- 1981-01-22 AT AT81300286T patent/ATE5563T1/en not_active IP Right Cessation
- 1981-01-22 DE DE8181300286T patent/DE3161605D1/en not_active Expired
- 1981-01-28 AU AU66647/81A patent/AU533491B2/en not_active Expired
- 1981-02-03 JP JP56014910A patent/JPS6055044B2/en not_active Expired
- 1981-02-03 CA CA000369935A patent/CA1144027A/en not_active Expired
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AU6664781A (en) | 1981-08-13 |
ATE5563T1 (en) | 1983-12-15 |
AU533491B2 (en) | 1983-11-24 |
DE3161605D1 (en) | 1984-01-19 |
EP0033615B1 (en) | 1983-12-14 |
JPS6055044B2 (en) | 1985-12-03 |
EP0033615A3 (en) | 1982-01-20 |
JPS56125311A (en) | 1981-10-01 |
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