Transdermal matrix system

• US 6,013,276 A
• Filed: 03/26/1998
• Issued: 01/11/2000
• Est. Priority Date: 09/27/1995
• Status: Expired due to Fees

• Current Assignee: Laboratoires D'Hygiene Et De Dietetique
• Original Assignee: Laboratoires D'Hygiene Et De Dietetique
• Inventors: Bevan, Bruno, Math, Marie-Christine, Teillaud, Eric
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): TRAN, SUSAN T
• Application Number:
  US09/043,760
• Time in Patent Office: 656 Days
• Field of Search: 424/448, 424/449, 424/443, 424/487
• US Class Current: 424/448
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 5/34 Gestagens

Abstract

A novel transdermal matrix system for the percutaneous delivery of a hormone, including a carrier and an adhesive matrix, is disclosed. The matrix includes (a) 39-61 parts by weight of an ethylene/vinyl acetate copolymer, (b) 12-17 parts by weight of 2-octyldodecyl myristate, (c) 5-17 parts by weight of diethyl phthalate, (d) 10-16 parts by weight of a compound selected from N-alkyl-2-pyrrolidones, wherein the alkyl group is a C_4-15 group, and (e) 1-12 parts by weight of at least one hormone selected from the group consisting of oestrogenic and progestogenic components. A method for preparing said transdermal matrix system and the therapeutical use of said system are also disclosed.

Claims

1. A transdermal matrix system for the transdermal administration of at least one hormone, said system having a carrier and an adhesive matrix, said matrix comprising:

(a) 39 to 61 parts by weight of ethylene/vinyl acetate copolymer,

(b) 12 to 17 parts by weight of 2-octyldodecyl myristate,

(c) 5 to 17 parts by weight of diethyl phthalate,

(d) 10 to 16 parts by weight of a compound selected from N-alkyl-2-pyrrolidones in which the alkyl group is a C₄ -C₁₅ group, and

(e) 1 to 12 parts by weight of at least one hormone selected from the group consisting of estrogen components and progestin components.

2. A transdermal matrix system according to claim 1 wherein said adhesive matrix also comprises 1 to 10 parts by weight of a vinyl acetate/N-vinyl-2-pyrrolidone (VA/VP) copolymer.

3. A transdermal matrix system according to claim 2 wherein the vinyl acetate/N-vinyl-2-pyrrolidone copolymer has a vinyl acetate content of between 30 and 70% by weight, based on the weight of the copolymer.

4. A transdermal matrix system according to claim 1 wherein the N-alkyl-2-pyrrolidone is N-dodecyl-2-pyrrolidone.

5. A transdermal matrix system according to claim 1 wherein the ethylene/vinyl acetate copolymer has a vinyl acetate content of between 30 and 75% by weight based on the weight of the copolymer.

6. A transdermal matrix system according to claim 1 wherein the hormone is an estrogen component.

7. A transdermal matrix system according to claim 1 wherein the hormone is a progestin component.

8. A transdermal matrix system according to claim 1 wherein the system contains a mixture of an estrogen component and a progestin component.

10. A method for treating the symptoms of menopause or osteoporosis using a transdermal matrix system according to any one of claims 1 to 8.

11. A system according to claim 2 wherein the matrix comprises the following for a total of 100 parts by weight:

54 parts by weight of ethylene/vinyl acetate copolymer;

17 parts by weight of 2-octyldodecyl myristate;

5 parts by weight of diethyl phthalate;

16 parts by weight of N-dodecyl-2-pyrrolidone;

2 parts by weight of 17β

-estradiol;

5 parts by weight of norethisterone acetate; and

1 part by weight of a vinyl acetate/N-vinyl-2-pyrrolidone (VA/VP) copolymer.

12. A system according to claim 2 wherein the matrix comprises the following for a total of 100 parts by weight:

62 parts by weight of ethylene/vinyl acetate copolymer;

13 parts by weight of 2-octyldodecyl myristate;

10 parts by weight of diethyl phthalate;

10 parts by weight of N-dodecyl-2-pyrrolidone;

3 parts by weight of 17β

-estradiol; and

2parts by weight of a vinyl acetate/N-vinyl-2-pyrrolidone (VA/VP) copolymer.

13. A system according to claim 2 the matrix comprises the following for a total of 100 parts by weight:

53 parts by weight of ethylene/vinyl acetate copolymer;

17 parts by weight of 2-octyldodecyl myristate;

10 parts by weight of diethyl phthalate;

13 parts by weight of N-dodecyl-2-pyrrolidone;

6 parts by weight of norethisterone acetate; and

1 part by weight of a vinyl acetate/N-vinyl-2-pyrrolidone (VA/VP) copolymer.

14. A transdermal matrix system according to claim 2 wherein the N-alkyl-2-pyrrolidone is N-dodecyl-2-pyrrolidone.

15. A transdermal matrix system according to claim 3 wherein the N-alkyl-2-pyrrolidone is N-dodecyl-2-pyrrolidone.

16. A transdermal matrix system according to claim 2 wherein the ethylene/vinyl acetate copolymer has a vinyl acetate content of between 30 and 75% by weight based on the weight of the copolymer.

17. A transdermal matrix system according to claim 3 wherein the ethylene/vinyl acetate copolymer has a vinyl acetate content of between 30 and 75% by weight based on the weight of the copolymer.

18. A transdermal matrix system according to claim 2 wherein the hormone is an estrogen component.

19. A transdermal matrix system according to claim 3 wherein the hormone is an estrogen component.

20. A transdermal matrix system according to claim 2 wherein the hormone is a progestin component.

21. A transdermal matrix system according to claim 3 wherein the hormone is a progestin component.

22. A transdermal matrix system according to claim 2 wherein the system contains a mixture of an estrogen component and a progestin component.

23. A transdermal matrix system according to claim 3 wherein the system contains a mixture of an estrogen component and a progestin component.

9. A method of preparing a transdermal matrix system comprising the steps of:

introducing diethyl phthalate, N-alkyl-2-pyrrolidone, 2-octyldodecyl myristate, at least one hormone selected from the group consisting of estrogen components, progestin components and mixtures thereof, optionally VA/VP copolymer, and EVA successively into a reactor to form a mixture and stirring the mixture;

incorporating a solvent or solvent system into the mixture at a temperature below the boiling point of the solvent or solvent system used and stirring, still at the same temperature, until the EVA has dissolved and said mixture has become homogeneous;

coating the homogeneous mixture onto a non-stick temporary carrier, at a temperature of between 50 and 70°

C., to give a deposit of 50 to 300 g/m² on said carrier;

heating the coating so as to evaporate the solvent to form a dry matrix; and

transferring the dry matrix to a final carrier.