Drospirenone-containing preparations for transdermal use

• US 20050222106A1
• Filed: 03/28/2005
• Published: 10/06/2005
• Est. Priority Date: 04/01/2004
• Status: Abandoned Application

• Current Assignee: Schering Ag (Merck & Co., Inc.)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Bracht, Stefan
• Application Number:
  US11/091,633
• Publication Number:
  US 20050222106A1
• Time in Patent Office: Days
• US Class Current: 514/177
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61K 9/7084 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

Abstract

The pharmaceutical preparation for transdermal administration contains solvent ingredients, such as water and ethanol and/or propanol, and drospirenone. The drospirenone is contained in the preparation in an amount that is not above its saturation solubility in an initial state prior to application to skin. However after application to the skin the amount of drospirenone exceeds its saturation solubility due to escape or discharge of the solvent ingredients from the preparation. Preferably the saturation solubility is exceeded by at least a factor of five during application to the skin. The pharmaceutical preparation can also contain an estrogen, such as ethinyl estradiol. It can be in the form of a semi-solid or liquid preparation that is contained in a reservoir-type transdermal patch. A transdermal patch for contraception containing the pharmaceutical preparation including drospirenone and ethinyl estradiol is also disclosed.

Claims

1. A pharmaceutical preparation for application to skin, said pharmaceutical preparation containing solvent ingredients and drospirenone, said drospirenone being present in the preparation in an amount such that a saturation solubility of the drospirenone is not exceed in the preparation in an initial state of the preparation prior to application of the preparation to the skin, but wherein said drospirenone is present in the preparation in other amounts such that the saturation solubility of the drospirenone is exceeded after application of the preparation to the skin because of escape or discharge of the solvent ingredients from the preparation.

2. The pharmaceutical preparation as defined in claim 1, wherein the saturation solubility of the drospirenone is exceeded by a factor of at least five during application to the skin.

3. The pharmaceutical preparation as defined in claim 2, wherein the saturation solubility of the drospirenone is exceed by a factor of at least 2 after one hour after application to the skin.

4. The pharmaceutical preparation as defined in claim 1, wherein the saturation solubility of the drospirenone is exceeded by a factor of at least 10 during application to the skin.

5. The pharmaceutical preparation as defined in claim 4, wherein the saturation solubility of the drospirenone is exceed by a factor of at least 5 after one hour after application to the skin.

6. The pharmaceutical preparation as defined in claim 1, wherein the solvent ingredients comprise ethanol and/or isopropanol.

7. The pharmaceutical preparation as defined in claim 1, further comprising an inhibiting additive for preventing crystallization of the drospirenone.

8. The pharmaceutical preparation as defined in claim 7, wherein the inhibiting additive comprises soluble polyvinyl pyrrolidone.

9. The pharmaceutical preparation as defined in claim 1, further comprising at least one permeation accelerant.

10. The pharmaceutical preparation as defined in claim 1, in the form of a semi-solid composition and said semi-solid composition consists of an alcohol-containing gel.

11. The pharmaceutical preparation as defined in claim 1, in the form of a liquid alcohol-containing composition and wherein said liquid alcohol-containing composition consists of a lotion, foam or a spray.

12. The pharmaceutical preparation as defined in claim 1, in the form of a liquid or semi-solid alcohol-containing composition, which is part of a reservoir-type transdermal patch.

13. The pharmaceutical preparation as defined in claim 12, wherein the saturation solubility of the drospirenone is exceeded by a factor of at least 1.5 during application to the skin.

14. The pharmaceutical preparation as defined in claim 12, wherein the saturation solubility of the drospirenone is exceeded by a factor of at least 2 during application to the skin.

15. The pharmaceutical preparation as defined in claim 12, wherein said liquid or semi-solid alcohol-containing composition has an alcohol content of at least 60% m/m.

16. The pharmaceutical preparation as defined in claim 12, wherein said liquid or semi-solid alcohol-containing composition has an alcohol content of at least 65% m/m.

17. The pharmaceutical preparation as defined in claim 1, further comprising an estrogen compound.

18. The pharmaceutical preparation as defined in claim 17, wherein said estrogen compound is present in an amount such that a saturation solubility of the estrogen compound is not exceeded in the preparation in the initial state prior to the application to the skin, but in an amount such that the saturation solubility of the estrogen compound is exceeded after application of the preparation to the skin due to escape or discharge of the solvent ingredients from the preparation.

19. The pharmaceutical preparation as defined in claim 18, wherein said estrogen compound is ethinyl estradiol.

20. A reservoir-type transdermal patch for contraception, said reservoir-type transdermal patch comprising a pharmaceutical preparation for transdermal administration, wherein said pharmaceutical preparation contains solvent ingredients and drospirenone, and said drospirenone is present in the preparation in an amount such that a saturation solubility of the drospirenone is not exceed in the preparation in an initial state of the preparation prior to application to the skin, but wherein said drospirenone is present in the preparation in other amounts such that the saturation solubility of the drospirenone is exceeded after application to the skin because of escape or discharge of the solvent ingredients from the preparation.

21. The reservoir-type transdermal patch as defined in claim 20, wherein the saturation solubility of the drospirenone is exceeded by a factor of at least 1.5 during application to the skin.

22. The reservoir-type transdermal patch as defined in claim 20, wherein the solvent ingredients comprise ethanol and/or isopropanol.

23. The reservoir-type transdermal patch as defined in claim 20, wherein the pharmaceutical composition includes an estrogen compound and wherein said estrogen compound is present in an amount such that a saturation solubility of the estrogen compound is not exceeded in the preparation in the initial state prior to the application to the skin, but in an amount such that the saturation solubility of the estrogen compound is exceeded after application to the skin due to escape or discharge of the solvent ingredients from the preparation.

24. The reservoir-type transdermal patch as defined in claim 20, wherein the estrogen compound is ethinyl estradiol.