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US5474783A Expired / Lapsed US ⏱️ 0.0 years remaining

Solubility parameter based drug delivery system and method for altering drug saturation concentration

Assignee: Noven Pharmaceuticals Inc
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Filing: 1991-06-27
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Granted: 1995-12-12
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Expires: 2011-06-27
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Abstract

Abstract The method of adjusting the saturation concentration of a drug in a transdermal composition for application to the dermis, which comprises mixing polymers having differing solubility parameters, so as to modulate the delivery of the drug. This results in the ability to achieve a predetermined permeation rate of the drug into and through the dermis. In one embodiment, a dermal composition of the present invention comprises a drug, an acrylate polymer, and a polysiloxane. The dermal compositions can be produced by a variety of methods known in the preparation of drug-containing adhesive preparations, including the mixing of the polymers, drug, and additional ingredients in solution, followed by removal of the processing solvents. The method and composition of this invention permit selectable loading of the drug into the dermal formulation and adjustment of the delivery rate of the drug from the composition through the dermis, while maintaining acceptable shear, tack, and peel adhesive properties.

Inventors

  • 👤 Jesus Miranda
  • 👤 Steven Sablotsky

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-26 07:16
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/70; A61K9/7023; A61K9/703; A61K9/7038; A61K9/7046; A61K9/7053; A61K47/00; A61K47/30; A61F; A61F13/00; A61F13/02; A61F13/0276; A61K9/7061; A61K9/7069; A61L; A61L15/00; A61L15/16; A61L15/18; A61L15/42; A61L15/58; A61L15/585; A61P; A61P11/00; A61P11/06; A61P25/00; A61P25/02; A61P27/00; A61P27/02; A61P27/06; A61P5/00; A61P5/24; A61P5/30; A61P9/00; A61P9/10; A61F2013/00361; A61F2013/00544; A61F2013/00646; B; B26; B26F; B26F1/00; B26F1/38; B26F1/384

Claims Analysis

Total Claims: 33
Claim 1
Independent Claim 316 words
A pressure sensitive adhesive transdermal drug delivery system comprising: (a) a blend consisting essentially of about 2% to about 96% by weight of a polyacrylate and about 98% to about 4% by weight of a polysiloxane, said blend being in an amount of about 99% to about 50% by weight of said system and wherein said ratio of polyacrylate to polysiloxane is from about 2:98 to about 86:14 by weight of said blend and wherein the permeation rate is controlled by varying the relative proportions of the polymers; (b) a drug in the amount of about 0.3% to about 50% by weight of said system and wherein the drug is selected from the group consisting of nitroglycerin, isosorbide dinitrate, isosorbide mononitrates, quinidine sulfate, procainamide, bendroflumethiazide, chlorothiazide, nifedipine, nicardipine, timolol, propranolol, verapamil, diltiazem, captopril, clonidine, prazosin, testosterone, estropipate, 17β-estradiol, 17β-estradiol valerate, equilin, mestranol, estrone, estriol, 17β-ethinyl estradiol, diethylstilbestrol, progesterone, 19-norprogesterone, norethindrone, norethindrone acetate, melengestrol, chloramdinone, ethisterone, medroxyprogesterone acetate, hydroxyprogesterone caproate, ethynodiol diacetate, norethynodrel, 17-alpha-hydroxyprogesterone, dydrogesterone, dimethisterone, ethinylestrenol, norgestrel, demegestone, promegestone, megestrol acetate, buprenorphine, naloxone, haloperidol, codeine, lidocaine, tetracaine, dyclonine, dibucaine, cocaine, procaine, mepivacaine, bupivacaine, etidocaine, prilocaine, benzocaine, fentanyl, hydrocortisone, cortisone, prednisolone, prednisone, halcinonide, betamethasone, ibuprophen, naproxen, fenoprofen, fenbufen, indoprofen, ketoprofen, suprofen, indomethacin, piroxicam, aspirin, salicylic acid, chlorpheniramine, theophilline, albuterol, terbutaline, metaproterenol, carbuterol, fenoterol, quinterenol, rimiterol, solmefamol, soterenol, tretoquinol, dopamine, phenylpropanolamine, epinephrine, pilocarpine, choline, acetylcholine, methacholine, carbachol, bethanechol, muscarine, arecoline, scopolamine, eucatropine, atropine, penicillin, tetracycline, papaverine, tamoxifen, dextroamphetamine, mazindol, alprazolam, chlordiazepoxide, clorazeptate, halazepam, oxazepam, prazepam, chlonazepam, flurazepam, triazolam, lorazepam, diazepam, thiopropazate, chlorpromazine, triflupromazine, mesoridazine, piperacetazine, thioridazine, acetophenazine, fluphenazine, perphenazine, trifluoperazine, chlorprothixene, thiothixene, bromperidol, loxapine, molindone, pyrimethamine, misoprostol, enprostil, levodopa, selegiline, baclofene, and mixtures thereof; (c) optionally, an effective amount of a co-solvent for the drug, said amount being up to about 30% by weight of said system; and (d) optionally, an effective amount of an enhancer, said amount being up to about 20% by weight of said system.
Claim 2
Dependent Claim 316 words
A pressure sensitive adhesive transdermal drug delivery system comprising: (a) a blend consisting essentially of about 2% to about 96% by weight of a polyacrylate and about 98% to about 4% by weight of a polysiloxane, said blend being in an amount of about 99% to about 50% by weight of said system and wherein said ratio of polyacrylate to polysiloxane is from about 2:98 to about 86:14 by weight of said blend and wherein the permeation rate is controlled by varying the relative proportions of the polymers; (b) a drug in the amount of about 0.3% to about 50% by weight of said system and wherein the drug is selected from the group consisting of nitroglycerin, isosorbide dinitrate, isosorbide mononitrates, quinidine sulfate, procainamide, bendroflumethiazide, chlorothiazide, nifedipine, nicardipine, timolol, propranolol, verapamil, diltiazem, captopril, clonidine, prazosin, testosterone, estropipate, 17β-estradiol, 17β-estradiol valerate, equilin, mestranol, estrone, estriol, 17β-ethinyl estradiol, diethylstilbestrol, progesterone, 19-norprogesterone, norethindrone, norethindrone acetate, melengestrol, chloramdinone, ethisterone, medroxyprogesterone acetate, hydroxyprogesterone caproate, ethynodiol diacetate, norethynodrel, 17-alpha-hydroxyprogesterone, dydrogesterone, dimethisterone, ethinylestrenol, norgestrel, demegestone, promegestone, megestrol acetate, buprenorphine, naloxone, haloperidol, codeine, lidocaine, tetracaine, dyclonine, dibucaine, cocaine, procaine, mepivacaine, bupivacaine, etidocaine, prilocaine, benzocaine, fentanyl, hydrocortisone, cortisone, prednisolone, prednisone, halcinonide, betamethasone, ibuprophen, naproxen, fenoprofen, fenbufen, indoprofen, ketoprofen, suprofen, indomethacin, piroxicam, aspirin, salicylic acid, chlorpheniramine, theophilline, albuterol, terbutaline, metaproterenol, carbuterol, fenoterol, quinterenol, rimiterol, solmefamol, soterenol, tretoquinol, dopamine, phenylpropanolamine, epinephrine, pilocarpine, choline, acetylcholine, methacholine, carbachol, bethanechol, muscarine, arecoline, scopolamine, eucatropine, atropine, penicillin, tetracycline, papaverine, tamoxifen, dextroamphetamine, mazindol, alprazolam, chlordiazepoxide, clorazeptate, halazepam, oxazepam, prazepam, chlonazepam, flurazepam, triazolam, lorazepam, diazepam, thiopropazate, chlorpromazine, triflupromazine, mesoridazine, piperacetazine, thioridazine, acetophenazine, fluphenazine, perphenazine, trifluoperazine, chlorprothixene, thiothixene, bromperidol, loxapine, molindone, pyrimethamine, misoprostol, enprostil, levodopa, selegiline, baclofene, and mixtures thereof; (c) optionally, an effective amount of a co-solvent for the drug, said amount being up to about 30% by weight of said system; and (d) optionally, an effective amount of an enhancer, said amount being up to about 20% by weight of said system.
Claim 3
Dependent Claim 30 words
The transdermal drug delivery system of claim 1 further comprising fillers and excipients in an amount of about 1% to about 15% by weight of said transdermal drug delivery system.
Claim 4
Dependent Claim 16 words
The transdermal drug delivery system of claim 1, which is in the form of a sheet.
Claim 5
Dependent Claim 34 words
The transdermal drug delivery system of claim 1, wherein the drug is a β 2 -adrenergic agonist selected from the group consisting of metaproterenol, terbutaline, albuterol, carbuterol, rimiterol, solmefamol, fenoterol, soterenol, tretoquinol, and quinterenol.
Claim 6
Dependent Claim 40 words
The transdermal drug delivery system of claim 4, wherein the β 2 -adrenergic agonist is albuterol and the albuterol is present in the transdermal drug delivery system in an amount of about 0.3% to less than about 30% by weight.
Claim 7
Dependent Claim 64 words
The transdermal drug delivery system of claim 4, which comprises based on the weight of the transdermal drug delivery system, about 0.3 to about 50% by weight of albuterol, about 14 to about 97% by weight of polysiloxane, about 2 to about 85% by weight of polyacrylate, 0 to about 20% by weight of enhancers, and 0 to about 30% by weight of cosolvents.
Claim 8
Dependent Claim 32 words
The transdermal drug delivery system of claim 1, wherein the drug is a tranquilizer selected from the group consisting of alprazolam, chlordiazepoxide, clorazeptate, halazepam, oxazepam, prazepam, chlonazepam, flurazepam, triazolam, lorazepam and diazepam.
Claim 9
Dependent Claim 13 words
The transdermal drug delivery system of claim 7, wherein the tranquilizer is alprazolam.
Claim 10
Dependent Claim 64 words
The transdermal drug delivery system of claim 8, which comprises based on the weight of the transdermal drug delivery system, about 0.3 to about 50% by weight of alprazolam, about 14 to about 97% by weight of polysiloxane, about 2 to about 85% by weight of polyacrylate, 0 to about 20% by weight of enhancers, and 0 to about 30% by weight of cosolvents.
Claim 11
Dependent Claim 64 words
The transdermal drug delivery system of claim 1, which comprises based on the weight of the transdermal drug delivery system, about 0.3 to about 50% by weight of drug, about 14 to about 97% by weight of polysiloxane, about 2 to about 85% by weight of polyacrylate, 0 to about 20% by weight of enhancers, and 0 to about 30% by weight of cosolvents.
Claim 12
Dependent Claim 14 words
The transdermal drug delivery system of claim 1 which further comprises a hydrophilic filler.
Claim 13
Dependent Claim 16 words
The transdermal drug delivery system of claim 11, wherein the hydrophilic filler comprises aluminum silicate clay.
Claim 14
Dependent Claim 20 words
The transdermal drug delivery system of claim 1, wherein the polyacrylate of the blend is itself a pressure sensitive adhesive.
Claim 15
Dependent Claim 33 words
The transdermal drug delivery system of claim 13 further comprising a backing material superimposed on one surface of the pressure sensitive adhesive, said backing material being substantially impermeable to the drug contained therein.
Claim 16
Dependent Claim 26 words
The transdermal drug delivery system of claim 13 further comprising a release liner superimposed on a surface of the pressure sensitive adhesive opposite said backing material.
Claim 17
Dependent Claim 46 words
The transdermal drug delivery system of claim 1 wherein the drug is a progestional agent selected from the group consisting of progesterone, 19-norprogesterone, norethindrone, norethindrone acetate, melengestrol, chloramdinone, ethisterone, medroxyprogesterone acetate, hydroxyprogesterone caproate, ethynodiol diacetate, norethynodrel, 17a-hydroxyprogesterone, dydrogesterone, dimethisterone, ethinylesternol, norgestrel, demegestone, promegestone, and megestrol acetate.
Claim 18
Dependent Claim 41 words
The transdermal drug delivery system of claim 1, wherein the drug is a cardioactive agent selected from the group consisting of nitroglycerin, isosorbide dinitrate, isosorbide monitrates, quinidine sulfate, procainamide, bendroflumethiazide, chlorothiazide, nifedipine, nicardipine, verapamil, dilatiazem, timolol, propranolol, captopril, clonidine and prazosin.
Claim 19
Dependent Claim 30 words
The transdermal drug delivery system of claim 1, wherein the drug is a cholinergic agonist selected from the group consisting of choline, acetylcholine, methacholine, carbachol, bethanechol, pilocarpine, muscarine, and arecoline.
Claim 20
Dependent Claim 34 words
The transdermal drug delivery system of claim 1, wherein the drug is 17β-estradiol and is present in the transdermal drug delivery system in an amount of from about 1% to about 5% by weight.
Claim 21
Dependent Claim 39 words
The transdermal drug delivery system of claim 16, wherein the progestational agent is norethindrone acetate and the norethindrone acetate is present in the transdermal drug delivery system in an amount of from about 1% to about 5% by weight.
Claim 22
Dependent Claim 38 words
The transdermal drug delivery system of claim 17, wherein the cardioactive agent is nitroglycerin and the nitroglycerin is present in the transdermal drug delivery system in an amount of about 0.3% to less than about 25% by weight.
Claim 23
Dependent Claim 38 words
The transdermal drug delivery system of claim 18, wherein the cholinergic agonist is pilocarpine and the pilocarpine is present in the transdermal drug delivery system in an amount of about 0.3% to less than about 30% by weight.
Claim 24
Dependent Claim 37 words
The transdermal drug delivery system of claim 1, wherein the drug is an antipsychotic selected from the group consisting of thiopropazate, chlorpromazine, triflupromazine, mesoridazine, piperacetazine, thioridazine, acetophenazine, fluphenazine, perphenazine, trifluoperazine, chlorprothixene, thiothixene, haloperidol, bromperidol, loxapine and molindone.
Claim 25
Dependent Claim 13 words
The transdermal drug delivery system of claim 23, wherein the antipsychotic is haloperidol.
Claim 26
Dependent Claim 32 words
The transdermal drug delivery system of claim 1, wherein the drug is an anesthetic selected from the group consisting of lidocaine, tetracaine, dyclonine, dibucaine, cocaine, procaine, mepivacaine, bupivacaine, etidocaine, prilocaine and benzocaine.
Claim 27
Dependent Claim 13 words
The transdermal drug delivery system of claim 25, wherein the anesthetic is lidocaine.
Claim 28
Dependent Claim 24 words
The transdermal drug delivery system of claim 1, wherein the drug is an analgesic selected from the group consisting of fentanyl, buprenorphine and codeine.
Claim 29
Dependent Claim 29 words
The transdermal drug delivery system of claim 1, wherein the drug is an estrogen selected from the group consisting of estropipate, 17β-estradiol, equilin, mestranol, estrone, estriol, estradiol, and diethylstilbestrol.
Claim 30
Dependent Claim 18 words
The transdermal drug delivery system of claim 28, comprising a mixture of a progestational agent and an estrogen.
Claim 31
Dependent Claim 44 words
The transdermal drug delivery system of claim 29, wherein said progestational agent is selected from the group consisting of progesterone, 19-norprogesterone, norethindrone, norethindrone acetate, melengestrol, chloromadinone, ethisterone, medroxyprogesterone acetate, hydroxyprogesterone caproate, ethynodiol diacetate, norethynodrel, 17a-hydroxyprogesterone, dydrogesterone, dimethisterone, ethinylestrenol, norgestrel, demegestone, promegestone, and megestrol acetate.
Claim 32
Dependent Claim 15 words
The transdermal drug delivery system of claim 30, wherein said progestational agent is norethindrone acetate.
Claim 33
Dependent Claim 13 words
The transdermal drug delivery system of claim 29, wherein said estrogen is 17β-estradiol.

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Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1998-12-11 1999-06-12 1999-12-12 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2002-12-11 2003-06-12 2003-12-12 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2006-12-11 2007-06-12 2007-12-12 $7700.00 Window Closed / Lapsed

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