Claims
- 1. A composition of matter useful for the delivery of a nonsteroidal antiinflammatory drug through a body surface, comprising a formulation of:
(a) a therapeutically effective amount of a nonsteroidal antiinflammatory drug; (b) a hydroxide-releasing agent in an amount effective to enhance the flux of the drug through the body surface without causing damage thereto and effective to provide a pH in the range of approximately 8.0 to 13 at the body surface, during drug administration; and wherein the amount of hydroxide-releasing agent in the formulation is the total of (a) the amount required to neutralize any acidic species in the formulation plus (b) an amount equal to approximately 0.5 to 25.0 wt % of the formulation; and (c) a pharmaceutically acceptable carrier suitable for topical or transdermal drug administration.
- 2. The composition of claim 1, wherein the pH at the body surface is in the range of approximately 8.0 to 11.5.
- 3. The composition of claim 2, wherein the pH at the body surface is in the range of approximately 8.5 to 11.5.
- 4. The composition of claim 1, wherein the formulation has a pH in the range of approximately 8.0 to 13.
- 5. The composition of claim 4, wherein the formulation has a pH in the range of approximately 8.0 to 11.5.
- 6. The composition of claim 5, having a pH in the range of approximately 8.5 to 11.5.
- 7. The composition of claim 1, wherein the carrier is aqueous.
- 8. The composition of claim 7, comprising a cream, a gel, a lotion, or paste.
- 9. The composition of claim 8, comprising a cream.
- 10. The composition of claim 8, comprising a gel.
- 11. The composition of claim 1, wherein the carrier is nonaqueous.
- 12. The composition of claim 11, comprising an ointment.
- 13. The composition of claim 1, wherein the composition is substantially free of additional permeation enhancers.
- 14. The composition of claim 1, wherein the composition is substantially free of organic solvents.
- 15. The composition of claim 1, wherein the hydroxide-releasing agent releases free hydroxide ions in the presence of an aqueous fluid.
- 16. The composition of claim 1, wherein the hydroxide-releasing agent is selected from the group consisting of inorganic hydroxides, inorganic oxides, metal salts of weak acids, and mixtures thereof.
- 17. The composition of claim 16, wherein the hydroxide-releasing agent is an inorganic hydroxide.
- 18. The composition of claim 17, wherein the inorganic hydroxide is selected from the group consisting of ammonium hydroxide, alkali metal hydroxides, alkaline earth metal hydroxides, and mixtures thereof.
- 19. The composition of claim 18, wherein the inorganic hydroxide is selected from the group consisting of ammonium hydroxide, sodium hydroxide, calcium hydroxide, potassium hydroxide, magnesium hydroxide, and mixtures thereof.
- 20. The composition of claim 19, wherein the inorganic hydroxide is selected from sodium hydroxide and potassium hydroxide.
- 21. The composition of claim 17, wherein the amount of inorganic hydroxide in the formulation is the total of (a) the amount required to neutralize any acidic species in the formulation plus (b) an amount equal to approximately 0.5 wt % to 4.0 wt % of the formulation.
- 22. The composition of claim 16, wherein the hydroxide-releasing agent is an inorganic oxide.
- 23. The composition of claim 22, wherein the inorganic oxide is selected from the group consisting of magnesium oxide, calcium oxide and mixtures thereof.
- 24. The composition of claim 22, wherein the formulation contains up to approximately 25 wt % of the hydroxide-releasing agent.
- 25. The composition of claim 16, wherein the hydroxide-releasing agent is a metal salt of a weak acid.
- 26. The composition of claim 25, wherein the hydroxide-releasing agent is selected from the group consisting of sodium acetate, sodium borate, sodium metaborate, sodium carbonate, sodium bicarbonate, tribasic sodium phosphate, dibasic sodium phosphate, potassium carbonate, potassium bicarbonate, potassium citrate, potassium acetate, dibasic potassium phosphate, tribasic potassium phosphate, dibasic ammonium phosphate, and mixtures thereof.
- 27. The composition of claim 25, wherein the formulation contains up to approximately 25 wt % of the hydroxide-releasing agent.
- 28. The composition of claim 1, wherein the drug is systemically acting.
- 29. The composition of claim 1, wherein the drug is a propionic acid derivative.
- 30. The composition of claim 29, wherein the propionic acid derivative is selected from the group consisting of ketoprofen, flurbiprofen, ibuprofen, naproxen, fenoprofen, benoxaprofen, indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen, suprofen, alminoprofen, butibufen, fenbufen, tiaprofenic acid, salts, esters, amides of any of the foregoing, and combinations thereof.
- 31. The composition of claim 30, wherein the propionic acid derivative is selected from the group consisting of ketoprofen and ibuprofen.
- 32. The composition of claim 1, wherein the drug is selected from the group consisting of acetylsalicylic acid, apazone, diclofenac, difenpiramide, diflunisal, etodolac, flufenamic acid, indomethacin, ketorolac, meclofenamate, mefenamic acid, nabumetone, phenylbutazone, piroxicam, salicylic acid, sulindac, tolmetin, salts, esters, amides of any of the foregoing, and combinations thereof.
- 33. The composition of claim 32, wherein the drug is selected from the group consisting of diclofenac, ketorolac, and piroxicam.
- 34. A system for the topical or transdermal administration of a nonsteroidal antiinflammatory drug, comprising:
(a) at least one drug reservoir containing the drug and a hydroxide-releasing agent in an amount effective to enhance the flux of the drug through the body surface without causing damage thereto and effective to provide a pH in the range of approximately 8.0 to 13 at the body surface during drug administration; and wherein the amount of hydroxide-releasing agent in the reservoir is the total of (a) the amount required to neutralize any acidic species in the reservoir plus (b) an amount equal to approximately 0.5 to 25.0 wt % of the reservoir; (b) a means for maintaining the system in drug and enhancer transmitting relationship to the body surface; and (c) a backing layer that serves as the outer surface of the system during use.
- 35. The system of claim 34, wherein the pH at the body surface is in the range of approximately 8.0 to 11.5.
- 36. The system of claim 35, wherein the pH at the body surface is in the range of approximately 8.5 to 11.5.
- 37. The system of claim 34, wherein the backing layer is occlusive.
- 38. The system of claim 37, wherein the drug reservoir is comprised of a polymeric adhesive.
- 39. The system of claim 38, wherein the polymeric adhesive serves as the means for maintaining the system in drug and enhancer transmitting relationship to the body service.
- 40. The system of claim 34, wherein the drug reservoir is comprised of a hydrogel.
- 41. The system of claim 34, wherein the drug reservoir is comprised of a sealed pouch containing the drug and hydroxide-releasing agent in a liquid or semi-solid formulation.
- 42. The system of claim 34, wherein the hydroxide-releasing agent is selected from the group consisting of inorganic hydroxides, inorganic oxides, metal salts of weak acids, and mixtures thereof.
- 43. The system of claim 42, wherein the hydroxide-releasing agent is an inorganic hydroxide.
- 44. The system of claim 43, wherein the inorganic hydroxide is selected from the group consisting of ammonium hydroxide, alkali metal hydroxides, alkaline earth metal hydroxides, and mixtures thereof.
- 45. The system of claim 44, wherein the inorganic hydroxide is selected from the group consisting of ammonium hydroxide, sodium hydroxide, calcium hydroxide, potassium hydroxide, magnesium hydroxide, and mixtures thereof.
- 46. The system of claim 45, wherein the inorganic hydroxide is selected from sodium hydroxide and potassium hydroxide.
- 47. The system of claim 42, wherein the hydroxide-releasing agent is an inorganic oxide.
- 48. The system of claim 47, wherein the inorganic oxide is selected from the group consisting of magnesium oxide, calcium oxide and mixtures thereof.
- 49. The system of claim 42, wherein the hydroxide-releasing agent is a metal salt of a weak acid.
- 50. The system of claim 49, wherein the hydroxide-releasing agent is selected from the group consisting of sodium acetate, sodium borate, sodium metaborate, sodium carbonate, sodium bicarbonate, tribasic sodium phosphate, dibasic sodium phosphate, potassium carbonate, potassium bicarbonate, potassium citrate, potassium acetate, dibasic potassium phosphate, tribasic potassium phosphate, dibasic ammonium phosphate, and mixtures thereof.
- 51. The system of claim 34, wherein the drug is systemically acting.
- 52. The system of claim 34, wherein the drug is a propionic acid derivative.
- 53. The system of claim 52, wherein the propionic acid derivative is selected from the group consisting of ketoprofen, flurbiprofen, ibuprofen, naproxen, fenoprofen, benoxaprofen, indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen, suprofen, alminoprofen, butibufen, fenbufen, tiaprofenic acid, salts, esters, amides of any of the foregoing, and combinations thereof.
- 54. The system of claim 53, wherein the propionic acid derivative is selected from the group consisting of ketoprofen and ibuprofen.
- 55. The system of claim 34, wherein the drug is selected from the group consisting of acetylsalicylic acid, apazone, diclofenac, difenpiramide, diflunisal, etodolac, flufenamic acid, indomethacin, ketorolac, meclofenamate, mefenamic acid, nabumetone, phenylbutazone, piroxicam, salicylic acid, sulindac, tolmetin, salts, esters, amides of any of the foregoing, and combinations thereof.
- 56. The system of claim 55, wherein the drug is selected from the group consisting of diclofenac, ketorolac, and piroxicam.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a divisional of U.S. Ser. No. 09/737,830, filed Dec. 14, 2000; which is a continuation-in-part of U.S. Ser. No. 09/569,889, filed May 11, 2000; which is a continuation-in part of U.S. Ser. No. 09/465,098, filed Dec. 16, 1999; the disclosures of which are incorporated by reference.
Divisions (1)
|
Number |
Date |
Country |
Parent |
09737830 |
Dec 2000 |
US |
Child |
10631539 |
Jul 2003 |
US |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
09569889 |
May 2000 |
US |
Child |
09737830 |
Dec 2000 |
US |
Parent |
09465098 |
Dec 1999 |
US |
Child |
09569889 |
May 2000 |
US |