Solid matrix system for transdermal drug delivery

• US 5,770,219 A
• Filed: 09/26/1994
• Issued: 06/23/1998
• Est. Priority Date: 09/08/1989
• Status: Expired due to Term

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Cygnus, Inc. (Johnson & Johnson)
• Inventors: Chiang, Chia-Ming, Tenzel, Renee Ann
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/311,914
• Time in Patent Office: 1,366 Days
• Field of Search: 424/448, 424/449
• 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 drug-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, said pressure-sensitive adhesive comprising an acetate acrylate copolymer and polyvinylpyrrolidone, said matrix being essentially free of a skin permeation enhancer.

2. The matrix of claim 1, wherein the estrogen is dispersed in the pressure sensitive adhesive in an amount at or below saturation.

3. The matrix of claim 1, wherein the acrylate copolymer comprises 2-ethylhexyl acrylate.

4. The matrix of claim 1, wherein the copolymer comprises at least one comonomer selected from the group consisting of vinyl acetate, acrylic acid and methyl acrylate.

5. The matrix of claim 4, wherein the copolymer comprises 2-ethylhexyl acrylate and vinyl acetate.

6. The matrix of claim 5, wherein the copolymer comprises approximately 72 wt % 2-ethylhexyl acrylate and approximately 28 wt % vinyl acetate.

7. The matrix of claim 3, wherein the copolymer comprises approximately 70 wt % 2-ethylhexyl acrylate and approximately 28 wt % vinyl acetate.

8. The matrix of claim 3, wherein the copolymer comprises approximately 85 wt % 2-ethylhexyl acrylate and approximately 10 wt % methyl acrylate, approximately 3 wt % acrylic acid and approximately 2 wt % vinyl acetate.

9. The matrix of claim 1, wherein the estrogen is selected from the group consisting of estradiol, ethinyl estradiol, esters of estradiol or a combination thereof.

10. The matrix of claim 1, further comprising a progestogen.

11. The matrix of claim 9 or 10, wherein the estrogen is estradiol.

12. The matrix of claim 9, wherein the estradiol ester is selected from the group consisting of estradiol valerate, estradiol cyprionate, estradiol decanoate and estradiol acetate.

13. The matrix of claim 11, wherein the progestogen is selected from the group consisting of norethindrone, norethindrone acetate, desogestrel, 3-keto desogestrel, gestadene and levonorgestrel.

14. The matrix of claim 13, wherein the progestogen is norethindrone acetate.

15. The matrix of claim 1, wherein the estrogen is estradiol.

16. The matrix of claim 10, wherein the estrogen is estradiol and the progestogen is norethindrone acetate.

17. The matrix of claim 1, wherein the copolymer comprises approximately 70 wt % 2-ethylhexyl acrylate and approximately 28 wt % vinyl acetate and the estrogen is estradiol.

18. The matrix of claim 10, wherein the copolymer comprises approximately 70 wt % 2-ethylhexyl acrylate and approximately 28 wt % vinyl acetate, the estrogen is estradiol and the progestogen is norethindrone acetate.

19. A transdermal or transmucosal drug delivery device for administering at least one steroid drug to an area of skin or mucosa comprising:

(a) a layer of backing material which is substantially impermeable to the drug and laminated thereto; and

(b) an adhesive drug-containing matrix as defined in any of claims 1, 10, 17 or 18.

20. A method for delivering a estrogen comprising applying the matrix of the device of claim 19 to the skin or mucosa of said patient.