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

• US 6,024,976 A
• Filed: 08/11/1997
• Issued: 02/15/2000
• Est. Priority Date: 03/04/1988
• Status: Expired due to Term

• Current Assignee: Noven Pharmaceuticals (Hisamitsu Pharmaceutical Company Incorporated)
• Original Assignee: Noven Pharmaceuticals (Hisamitsu Pharmaceutical Company Incorporated)
• Inventors: Miranda, Jesus, Sablotsky, Steven
• Primary Examiner(s): VENKAT, JYOTHSNA A
• Application Number:
  US08/907,906
• Time in Patent Office: 918 Days
• Field of Search: 424/448, 424/449
• US Class Current: 424/449
• CPC Class Codes: A61F 13/0276 Apparatus or processes for manufacturing adhesive dressings or bandages
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: A61L 15/18 containing inorganic materials
• CPC Class Codes: A61L 15/58 Adhesives
• CPC Class Codes: A61L 15/585 Mixtures of macromolecular compounds
• CPC Class Codes: B26F 1/384 using rotating drums
• CPC Class Codes: C08L 31/04 Homopolymers or copolymers of vinyl acetate
• CPC Class Codes: C08L 33/00 Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers

Abstract

A blend of at least two polymers, or at least one polymer and a soluble polyvinylpyrrolidone, in combination with a drug provides a pressure-sensitive adhesive composition for a transdermal drug delivery system in which the drug is delivered from the pressure-sensitive adhesive composition and through dermis when the pressure-sensitive adhesive composition is in contact with human skin. According to the invention, soluble polyvinylpyrrolidone can be used to prevent crystallization of the drug, without affecting the rate of drug delivery from the pressure-sensitive adhesive composition.

Claims

1. A transdermal drug delivery system comprising a pressure-sensitive adhesive composition, wherein said composition comprises a blend of (1) a synthetic elastomeric polymer;

(2) a soluble PVP and (3) at least one drug.

2. A transdermal drug delivery system according to claim 1, wherein said synthetic elastomeric Polymer is a polysiloxane.

3. A transdermal drug delivery system according to claim 1, wherein said blend further contains at least one enhancer.

4. The composition of claim 1, comprising about 5%-90% silicone adhesive, about 1%-30% polyvinylpyrrolidone, about 1%-25% dipropylene glycol, about 0.5%-10% oleic acid and about 1%-10% alprazolam based on dry weight of the total composition.

5. The composition of claim 1, comprising about 25%-75% silicone adhesive, about 5%-50% acrylic adhesive, about 5%-25% polyvinylpyrrolidone, about 2%-8% dipropylene glycol, about 2%-6% oleyl alcohol and about 1%-20% clonazepam based on dry weight of the total composition.

6. The composition of claim 1, comprising about 5%-90% silicone adhesive, about 5%-90% acrylic adhesive, about 1%-20% polyvinylpyrrolidone, about 1%-10% clonidine based on dry weight of the total composition.

7. The composition of claim 1, comprising about 40%-85% silicone adhesive, about 2.5%-20% acrylic adhesive, about 5.0%-15% polyvinylpyrrolidone, about 2%-10% dipropylene glycol, about 2%-10% oleyl alochol and about 0.5%-5.0% fludrocortisone acetate based on dry weight of the total composition.

8. The composition of claim 1, comprising about 5%-75% acrylic adhesive, about 5%-75% silicone adhesive, about 2%-25% polyvinylpyrrolidone, about 2%-25% oleic acid and about 5%-20% keptprofen based on dry weight of the total composition.

9. The composition of claim 1, comprising about 1%-65% silicone adhesive, about 5%-70% acrylic adhesive, about 1%-15% polyvinylpyrrolidone, and about 5%-30% methylphenidate based on dry weight of the total composition.

10. The composition of claim 1, comprising about 1%-70% silicone adhesive, about 5%-70% acrylic adhesive, about 2%-20% polyvinylpyrrolidone, and about 5%-30% methylphenidate based on dry weight of the total composition.

11. The composition of claim 1, comprising about 5%-75% silicone adhesive, about 10%-50% acrylic adhesive, about 5%-20% polyvinylpyrrolidone, and about 0.5%-20% terbinafine based on dry weight of the total composition.

12. The composition of claim 1, comprising about 40%-70% silicone adhesive, about 5%-30% acrtylic adhesive, about 2%-15% polyvinylpyrrolidone, about 0%-10% dipropylene glycol, about 0%-10% oleyl alcohol and about 1%-10% estradiol based on dry weight of the total composition.

13. A transdermal drug delivery system comprising a pressure-sensitive adhesive composition, wherein said composition comprises a blend of (1) a synthetic elastomeric polymer, (2) a polyacrylate polymer, (3) a soluble PVP and (4) at least one drug.

14. The transdermal drug delivery system of claim 13 which is in a defined geometric shape.

15. The transdermal drug delivery system of claim 14 which is in the form of a sheet.

16. The transdermal drug delivery system of claim 14 which is in the form of an individual dosage unit.

17. The transdermal drug delivery system of claim 13 further comprising a backing material superimposed on one surface of said pressure sensitive adhesive composition, said backing material being substantially impermeable to said drug contained therein.

18. The transdermal drug delivery system of claim 17 further comprising a release liner superimposed on a surface of said pressure sensitive adhesive composition opposite said backing material.

19. The transdermal drug delivery system of claim 13, wherein said system is a reservoir device having an adhesive portion comprised of said blend.

20. The transdermal drug delivery system according to claim 13, wherein said synthetic elastomeric polymer is present in said system from about 14% to about 94% by weight of the total pressure-sensitive adhesive composition.

21. The transdermal delivery system according to claim 20, wherein said synthetic elastomeric polymer is polysiloxane.

22. The transdermal drug delivery system according to claim 13, wherein said polyacrylate polymer is present in said system from about 5% to about 85% by weight of the total pressure-sensitive adhesive composition.

23. The transdermal drug delivery system according to claim 13, wherein said synthetic elastomeric polymer and said polyacrylate polymer differ in solubility parameter by an increment of at least 2 (J/cm³)^1/2.

24. The transdermal drug delivery system according to claim 13, wherein said soluble PVP is present in said system from about 1% to about 20% by weight of the total pressure-sensitive adhesive composition.

25. The transdermal drug delivery system according to claim 24, wherein said soluble PVP has a molecular weight from about 44,000 to 54,000.

26. The transdermal drug delivery system according to claim 13, wherein said drug is present in said system from about 0.1% to about 50% by weight of the total pressure-sensitive adhesive composition.

27. The transdermal drug delivery system according to claim 13, wherein said blend further contains at least one enhancer.

28. The transdermal drug delivery system according to claim 27, wherein said enhancer is present in said system from about 1% to about 20% by weight of the total pressure-sensitive adhesive composition.

29. The transdermal drug delivery system of claim 13, further comprising a clay.

30. The transdermal drug delivery system of claim 29, wherein said clay is bentonite.

31. The transdermal drug delivery system of claim 13, wherein said drug is a steroid.

32. The transdermal drug delivery system of claim 31, wherein said steroid is an estrogen selected from the group consisting of conjugated estrogens, esterified estrogens, estropipate, 17β

-estradiol, equilin, mestranol, estrone, estriol, ethinyl estradiol and diethylstilbestrol.

33. The transdermal drug delivery system of claim 32, wherein said estrogen is 17β

-estradiol, and wherein said 17β

-estradiol is present in said system in an amount of from about 0.1% to about 5% by weight.

34. The transdermal drug delivery system of claim 31, wherein said steroid is a progestational agent.

35. The transdermal drug delivery system of claim 34, wherein said progestational agent is selected from the group consisting of progesterone, 19-norprogesterone, norethindrone, norethindrone acetate, melengestrol, chlormadinone, ethisterone, medroxyprogesterone acetate, hydroxyprogesterone caproate, ethynodiol diacetate, norethynodrel, 17α

-hydroxyprogesterone, dydrogesterone, dimethisterone, ethinylestrenol, norgestrel, demegestone, promegestone and megestrol acetate.

36. The transdermal drug delivery system of claim 35, wherein said progestational agent is norethindrone acetate, and wherein said norethindrone acetate is present in said system in an amount of from about 1% to about 5% by weight.

37. The transdermal drug delivery system of claim 31, wherein said system comprises a mixture of a progestational agent and an estrogen.

38. The transdermal drug delivery system of claim 37, wherein said progestational agent is selected from the group consisting of progesterone, 19-norprogesterone, norethindrone, norethindrone acetate, melengestrol, chlormadinone, ethisterone, medroxyprogesterone acetate, hydroxyprogesterone caproate, ethynodiol diacetate, norethynodrel, 17α

-hydroxyprogesterone, dydrogesterone, dimethisterone, ethinylestrenol, norgestrel, demegestone, promegestone and megestrol acetate.

39. The transdermal drug delivery system of claim 38, wherein said progestational agent is norethindrone acetate.

40. The transdermal drug delivery system of claim 37, wherein said estrogen is selected from the group consisting of conjugated estrogens, esterified estrogens, estropipate, 17β

-estradiol, equilin, mestranol, estrone, estriol, ethinyl estradiol and diethylstilbestrol.

41. The transdermal drug delivery system of claim 40, wherein said estrogen is 17β

-estradiol.

42. The transdermal drug delivery system of claim 13, wherein said drug is a β

₂ -adrenergic agonist.

43. The transdermal drug delivery system of claim 42, wherein said β

₂ -adrenergic agonist is selected from the group consisting of metaproterenol, terbutaline, albuterol, carbuterol, rimiterol, salmefamol, fenoterol, soterenol, tratoquinol and quinterenol.

44. The transdermal drug delivery system of claim 43, wherein said β

₂ -adrenergic agonist is albuterol, and wherein said albuterol is present in the system in an amount of less than about 30% by weight.

45. The transdermal drug delivery system of claim 13, wherein said drug is a cardioactive agent.

46. The transdermal drug delivery system of claim 45, wherein said cardioactive agent is selected from the group consisting of nitroglycerin, isosorbide dinitrate, isosorbide mononitrates, quinidine sulfate, procainamide, benzydroflumethiazide, bendroflumethiazide, chlorothiazide, nifedipine, nicardipine, verapamil, diltiazem, timolol, propranolol, captopril, clonidine and prazosin.

47. The transdermal drug delivery system of claim 46, wherein the cardioactive agent is nitroglycerin, and wherein said nitroglycerin is present in said system in an amount of less than about 25% by weight.

48. The transdermal drug delivery system of claim 13, wherein said drug is a cholinergic agonist.

49. The transdermal drug delivery system of claim 48, wherein said cholinergic agonist is selected from the group consisting of choline, acetylcholine, methacholine, carbachol, bethanechol, pilocarpine, muscarine and arecoline.

50. The transdermal drug delivery system of claim 49, wherein said cholinergic agonist is pilocarpine, and wherein said pilocarpine is present in said system in an amount of less than about 30% by weight.

51. The transdermal drug delivery system of claim 13, wherein said drug is a tranquilizer.

52. The transdermal drug delivery system of claim 51, wherein said tranquilizer is selected from the group consisting of alprazolam, chlordiazepoxide, clorazeptate, halazepam, oxazepam, prazepam, clonazepam, flurazepam, triazolam, lorazepam and diazepam.

53. The transdermal drug delivery system of claim 52, wherein said tranquilizer is alprazolam.

54. The transdermal drug delivery system of claim 13, wherein said drug is an antipsychotic.

55. The transdermal drug delivery system of claim 54, wherein said antipsychotic is selected from the group consisting of thiopropazate, chlorpromazine, triflupromazine, mesoridazine, piperacetazine, thioridazine, acetophenazine, fluphenazine, perphenazine, trifluoperazine, chlorprathixene, thiothixene, haloperidol, bromperidol, loxapine and molindone.

56. The transdermal drug delivery system of claim 55, wherein said antipsychotic is haloperidol.

57. The transdermal drug delivery system of claim 13, wherein said drug is an anesthetic.

58. The transdermal drug delivery system of claim 57, wherein said anesthetic is selected from the group consisting of lidocaine, tetracaine, dyclonine, dibucaine, cocaine, procaine, mepivacaine, bupivacaine, etidocaine, prilocaine and benzocaine.

59. The transdermal drug delivery system of claim 58, wherein said anesthetic is lidocaine.

60. The transdermal drug delivery system of claim 13, wherein said drug is an analgesic.

61. The transdermal drug delivery system of claim 60, wherein said analgesic is selected from the group consisting of fentanyl, buprenorphine and codeine.

62. The transdermal drug delivery system of claim 13, wherein said drug has an action on the central nervous system.

63. The transdermal drug delivery system of claim 62, wherein said drug is nicotine.

64. The transdermal drug delivery system of claim 13, wherein said drug is a vasodilator.

65. The transdermal drug delivery system of claim 64, wherein said drug is papaverine.

66. The transdermal drug delivery system of claim 13, comprising at least two drugs.