Transdermal matrix system

• US 6,007,835 A
• Filed: 03/26/1998
• Issued: 12/28/1999
• 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: Dhuique-Mayer, Daniel, Bon-Lapillonne, Chantal, Mikler, Claude
• Primary Examiner(s): Harrison, Robert H.
• Application Number:
  US09/043,726
• Time in Patent Office: 642 Days
• Field of Search: 424/448, 424/449
• 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: A61K 9/7076 the adhesive comprising ingredients of undetermined constitution or reaction products thereof, e.g. rosin or other plant resins

Abstract

A novel transdermal system for the percutaneous delivery of a hormone, including a carrier and an adhesive matrix, is disclosed. The matrix includes (a) 20-50 parts by weight of a poly(styrene-isoprene-styrene) triblock copolymer, (b) 30-60 parts by weight of a tackifyier resin, (c) 4-25 parts by weight of propylene glycol laurate, (d) 2-10 parts by weight of a compound selected from N-alkyl-2-pyrrolidones, wherein the alkyl group is a C_4-- C₁₅ group, (e) 0.01-2 parts by weight of a stabilizing agent, (f) 0.1-12 parts by weight of at least one hormone selected from the group consisting of oestrogenic and progestogenic components, and (g) 1-12 parts by weight of a vinyl acetate/N-vinyl-2-pyrrolidone copolymer. A method for preparing said system and the therapeutical use thereof are also disclosed.

Claims

1. A transdermal matrix system for the percutaneous administration of at least one hormone, said matrix system having a support and an adhesive matrix wherein said matrix comprises:

(a) 20 to 50 parts by weight of a poly(styrene-isoprene-styrene) triblock (SIS) copolymer,

(b) 30 to 60 parts by weight of a tackifying resin,

(c) 4 to 25 parts by weight of propylene glycol laurate,

(d) 2 to 10 parts by weight of an N-alkyl-2-pyrrolidone compound in which the alkyl group is a C₄ --C₁₅ group,

(e) 0.1 to 2 parts by weight of a stabilizing agent,

(f) 0.1 to 12 parts by weight of at least one hormone selected from the group consisting of oestrogen compounds and progestogen compounds, and

(g) 1 to 12 parts by weight of a vinyl acetate/N-vinyl-2-pyrrolidone (VA/VP) copolymer.

2. The transdermal matrix system according to claim 1 wherein the N-alkyl-2-pyrrolidone compound is N-octyl-2-pyrrolidone.

3. The 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 relative to the weight of the said copolymer.

4. The transdermal matrix system according to claim 1 wherein the poly(styrene-isoprene-styrene) triblock copolymer has a styrene content of between 14 and 50% by weight relative to the weight of said copolymer.

5. The transdermal matrix system according to claim 1 wherein the poly(styrene-isoprene-styrene) triblock copolymer has a styrene content of between 17 and 47% by weight relative to the weight of said copolymer.

6. The transdermal matrix system according to claim 1 wherein the hormone is an oestrogen compound.

7. The transdermal matrix system according to claim 6 wherein said oestrogen compound is 17β

-oestradiol.

8. The transdermal matrix system according to claim 1 wherein the hormone is a progestogen compound.

9. The transdermal matrix system according to claim 8 wherein said progestrogen compound is norethisterone acetate.

10. The transdermal matrix system according to claim 1 wherein the matrix contains a mixture of an oestrogen compound and a progestogen compound.

11. The transdermal matrix system according to claim 10 wherein said oestrogen compound is 17β

-oestradiol and said progestrogen compound is norethisterone acetate.

12. A method for preparing a transdermal matrix system according to claim 1 said method comprising the steps of:

(α

) introducing, with stirring, into a reactor containing a solvent for an SIS copolymer, at a temperature below the boiling temperature of said solvent, at least one hormone selected from the group consisting of oestrogen compounds and progestogen compounds, a stabilizing agent, a VA/VP copolymer, an N-alkyl-2-pyrrolidone compound and propylene glycol laurate and then homogenizing the resulting mixture,

(β

) incorporating into the mixture thus obtained an SIS copolymer and a tackifying resin and stirring, still at the same temperature, until complete dissolution of the constituents and complete homogenization of the mixture;

(γ

) coating the homogeneous mixture thus obtained, at room temperature, onto a temporary anti-adherent support so as to obtain a coating of 50 to 300 g/m² on the said support; and

,

(δ

) evaporating the solvent by heating said coating at a temperature greater than the boiling point of said solvent, and then transferring said coating onto a permanent support.

13. A method for preparing a transdermal matrix system according to claim 1, said method comprising the steps of:

(α

) mixing an SIS copolymer, a stabilizing agent and a tackifying resin at a temperature greater than 110°

C. and then homogenizing the resulting mixture;

(β

) incorporating into the homogeneous mixture thus obtained propylene glycol laurate, an N-alkyl-2-pyrrolidone compound and a VA/VP copolymer, at a temperature of between 80 and 110°

C., and the homogenizing the resulting mixture;

(γ

) incorporating into the homogeneous mixture thus obtained at least one hormone selected from the group consisting of oestrogen compounds and progestogen compounds, and then homogenizing the resulting mixture;

(δ

) coating the homogeneous mixture thus obtained, at a temperature of between 80 and 130°

C., onto a temporary anti-adherent support so as to obtain a coating of 50 to 300 g/m² on the said support; and

,

(ε

) transferring said coating onto a permanent support.

14. A method for the treatment of menopause symptoms comprising applying to the skin of a patient in need of such a treatment a transdermal matrix system according to claim 1 which contains a therapeutically effective amount of at least one hormone selected from the group consisting of oestrogen compounds and progestrogen compounds.

15. A method for the treatment of osteoporosis symptoms comprising applying to the skin of a patient in need of such a treatment a transdermal matrix system according to claim 1 which contains a therapeutically effective amount of at least one hormone selected from the group consisting of oestrogen compounds and progestrogen compounds.

16. The transdermal matrix system according to claim 1 wherein the matrix comprises, for a total of 100 parts by weight:

(a) 31.3 parts by weight of SIS copolymer,

(b) 44 parts by weight of tackifying resin,

(c) 10.5 parts by weight of propylene glycol laurate,

(d) 4 parts by weight of N-octyl-2-pyrrolidone,

(e) 0.2 part by weight of a stabilizing agent,

(f) 4 parts by weight of norethisterone acetate, and

(g) 6 parts by weight of a vinyl acetate/N-vinyl-2-pyrrolidone (VA/VP) copolymer.

17. The transdermal matrix system according to claim 1 wherein the matrix comprises, for a total of 100 parts by weight:

(a) 37.8 parts by weight of SIS copolymer,

(b) 38 parts by weight of a tackifying resin,

(c) 15 parts by weight of propylene glycol laurate.

(d) 4 parts by weight of N-octyl-2-pyrrolidone,

(e) 0.2 part by weight of a stabilizing agent,

(f) 1 part by weight of 17β

-oestradiol, and

(g) 4 parts by weight of a vinyl acetate/N-vinyl-2-pyrrolidone (VA/VP) copolymer.

18. The transdermal matrix system according to claim 1 wherein the matrix compsirse, for a total of 100 parts by weight:

(a) 34.3 parts by weight of SIS copolymer,

(b) 41 parts by weight of a tackifying resin,

(c) 14 parts by weight of propylene glycol laurate,

(d) 4 parts by weight of N-octyl-2-pyrrolidone,

(e) 0.2 part by weight of a stabilizing agent,

(f₁) 0.5 part by weight of 17β

-oestradio,

(f₂) 3 parts by weight of norethisterone acetate, and

(g) 3 parts by weight of a vinyl acetate/N-vinyl-2-pyrrolidone (VA/VP) copolymer.