Solid matrix system for transdermal drug delivery

• US 6,149,935 A
• Filed: 08/16/1999
• Issued: 11/21/2000
• Est. Priority Date: 09/08/1989
• Status: Expired due to Term

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Inventors: Tenzel, Renee Ann, Chiang, Chia-Ming
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): GHALI, ISIS A D
• Application Number:
  US09/375,837
• Time in Patent Office: 463 Days
• Field of Search: 424/448, 424/449, 424/443, 424/485
• US Class Current: 424/448
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• 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 9/7053 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

Abstract

A matrix for containing drugs for transdermal delivery systems is disclosed. The matrix, formed of a skin-adhesive acrylate copolymer, attains high rates of drug delivery without the addition of drug delivery rate enhancers. In preferred embodiments the matrix is used to administer steroids, in particular estradiol. Water-soluble polymers may be added as well.

Claims

1. A method for making an estrogen-containing matrix for use in a transdermal drug delivery device for administering at least one estrogen to an area of skin or mucosa, comprising the estrogen dispersed in a body of a pressure sensitive adhesive, the method comprising:

a) incorporating an estrogen into a pressure sensitive adhesive material and a volatile solvent, to form a homogeneous solution or slurry;

b) casting the homogeneous solution or slurry; and

c) evaporating the volatile solvent from the homogeneous solution or slurry to form a solid matrix,

wherein the pressure sensitive adhesive comprises an acrylate copolymer and polyvinylpyrrolidone, said matrix being essentially free of a skin permeation enhancer.

2. The method of claim 1, wherein incorporating comprises dissolving the estrogen in the solution or slurry of the pressure sensitive adhesive material and the volatile solvent.

3. The method of claim 1, wherein incorporating comprises finely dispersing the estrogen in the homogeneous solution or slurry of the pressure sensitive adhesive material and the volatile solvent.

4. The method of claim 1, wherein incorporating comprises mixing the estrogen with the volatile solvent prior to adding the pressure sensitive adhesive material.

5. The method of claim 1, wherein the solid matrix comprises a layer between 10 micrometers and about 250 micrometers in thickness.

6. The method of claim 5, wherein the solid matrix comprises a layer between 15 micrometers and 100 micrometers in thickness.

7. The method of claim 1, wherein evaporating comprises a technique selected from the group consisting of heat, air flow, vacuum, and combinations thereof.

8. The method of claim 7, wherein evaporating is carried out between room temperature and about 100°

C.

9. The method of claim 7, wherein evaporating is carried out until less than 5 wt % of the volatile solvent remains in the matrix.

10. The method of claim 9, wherein evaporating is carried out until less than 1 wt % of the volatile solvent remains in the matrix.

11. The method of claim 1, further comprising (d) laminating the solid matrix onto a release liner.

12. The method of claim 1, wherein the pressure sensitive adhesive material comprises a copolymer of 2-ethylhexyl acrylate and at least one copolymer selected from the group consisting of methyl acrylate, acrylic acid, and vinyl acetate.

13. The method of claim 12, wherein the pressure sensitive adhesive material comprises approximately 70 wt % 2-ethylhexyl acrylate and approximately 30 wt % vinyl acetate.

14. The method of claim 12, wherein the pressure sensitive adhesive material comprises approximately 72 wt % 2-ethylhexyl acrylate and approximately 28 wt % vinyl acetate.

15. The method of claim 12, wherein the pressure sensitive adhesive material comprises approximately 85 wt % 2-ethylhexyl acrylate, 10 wt % methyl acrylate, 3 wt % acrylic acid, and 2 wt % vinyl acetate.

16. The method of claim 1, wherein the estrogen is selected from the group consisting of estradiol, estradiol valerate, estradiol cyprionate, estradiol decanoate, estradiol acetate, and ethinyl estradiol.

17. The method of claim 1, wherein the homogeneous solution or slurry further comprises a progestogen.

18. The method of claim 17, wherein the progestogen is selected from the group consisting of norethindrone, norethindrone acetate, desogestrel, 3-keto desogestrel, gestadene, and levonorgestrel.

19. The method of claim 1, wherein the pressure sensitive adhesive material further comprises a water-soluble polymer.

20. The method of claim 19, wherein the water soluble polymer comprises polyvinylpyrrolidone.

21. The method of claim 19, wherein the water soluble polymer comprises polyvinylalcohol.