Solid matrix system for transdermal drug delivery

• US 5,252,334 A
• Filed: 03/20/1992
• Issued: 10/12/1993
• Est. Priority Date: 09/08/1989
• Status: Expired due to Term

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Cygnus Therapeutic Systems
• Inventors: Tenzel, Renee A., Chiang, Chia-Ming
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HORNE, LEON
• Application Number:
  US07/857,094
• Time in Patent Office: 571 Days
• Field of Search: 424/447, 424/448, 424/449, 424/443
• 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 transdermal drug delivery device for administering at least one steroid drug to an area of skin or mucosa, wherein the device consists of a first layer laminated to a second layer, wherein

said first layer consists of a layer of a backing material which is substantially impermeable to the at least one steroid drug;

and

said second layer consists essentially of a therapeutically effective amount of the at least one steroid drug, and an adhesive matrix wherein said second layer is essentially free of a skin penetration rate enhancer, and wherein the adhesive matrix comprises a copolymer of 2-ethylhexyl acrylate and at least one comonmer selected from the group consisting of vinyl acetate, acrylic acid, and methyl acrylate.

2. The device of claim 1, wherein the adhesive resin comprises a copolymer of 2-ethylhexyl acrylate and vinyl acetate.

3. The device of claim 2, wherein the copolymer comprises approximately 70 wt. % 2-ethylhexyl acrylate and approximately 30 wt. % vinyl acetate.

4. The device of claim 2, wherein the copolymer comprises approximately 72 wt. % 2-ethylhexyl acrylate and approximately 28 wt. % vinyl acetate.

5. The device of claim 1, wherein the adhesive matrix comprises a first copolymer of approximately 70 wt. % 2-ethylhexyl acrylate and approximately 30 wt. % vinyl acetate, and a second copolymer of approximately 72 wt. % 2-ethylhexyl acrylate and approximately 28 wt. % vinyl acetate.

6. The device of claim 1, wherein the adhesive matrix comprises a copolymer of 2-ethylhexylacrylate, methyl acrylate, acrylic acid, and vinyl acetate.

7. The device of claim 6, wherein the adhesive resin comprises approximately 85 wt. % 2-ethylhexyl acrylate, 10 wt. % methyl acrylate, 3 wt. % acrylic acid, and 2 wt. % vinyl acrylate.

8. The device of claim 1, wherein the steroid drug is an estrogen.

9. The device of claim 8, wherein the estrogen is estradiol.

10. The device of claim 1, wherein the steroid drug is s progestogen.

11. The device of claim 10, wherein the progestogen comprises norethindrone or norethindrone acetate.

12. The device of claim 1, wherein the drug comprises a mixture of an estrogen and a progestogen.

16. The device according to claim 1 wherein the drug is dissolved in the matrix.

17. The device according to claim 1 wherein the drug is dispersed in the matrix.

18. The device according to claim 8 wherein the estrogen is ethinyl estradiol.

19. The device according to claim 1 wherein the steroid drug is present in a concentration below the saturation amount.

20. The device according to claim 1 wherein the steroid drug is present in a concentration at the saturation amount.

21. The device according to claim 1 wherein the steroid drug is present in a concentration above the saturation amount.

22. The transdermal drug delivery device according to claim 1 wherein the device is of from about 0.5 cm² to 100 cm².

23. The transdermal drug delivery device according to claim 1 wherein the drug is present in an amount of from about 0.5% to about 25% of the total matrix weight.

13. A transdermal drug delivery device for administering at least one steroid drug to an area of skin or mucosa, wherein the device consists of a first layer laminated to a second layer, wherein

said first layer consists of a layer of a backing material which is substantially impermeable to the at least one steroid drug;

and

said second layer consists essentially of a therapeutically effective amount of the at least one steroid drug and an adhesive matrix, wherein said second layer is essentially free of a skin penetration rate enhancer, and wherein the adhesive matrix comprises a water soluble polymer, a copolymer of 2-ethylhexyl acrylate and at least one comonomer selected from the group consisting of vinyl acetate, acrylic acid, and methyl acrylate.

24. The device of claim 13, wherein the water-soluble polymer is polyvinyl alcohol.

25. The device according to claim 13 wherein the water soluble polymer is polyvinyl pyrrolidone.

14. A transdermal drug delivery device for administering at least one steroid drug to an area of skin or mucosa, wherein the device consists of:

(a) a layer of backing material which is substantially impermeable to the at least one steroid drug;

(b) a matrix layer essentially free of a skin penetration rate enhancer said matrix consisting essentially of a therapeutically effective amount of the at least one steroid drug and a body of an adhesive resin, and wherein the adhesive resin comprises a copolymer of 2-ethylhexyl acrylate and at least one comonomer selected from the group consisting of vinyl acetate, acrylic acid, and methyl acrylate; and

(c) between the backing material and matrix, a drug reservoir for delivering additional amounts of the at least one steroid drug to the adhesive matrix.

15. The device of claim 14, wherein a polymer of the matrix is a water-soluble polymer.