Styrene-isoprene-styrene copolymer-based transdermal matrix system for the administration of an oestrogen and/or a progestogen

• US 5,580,572 A
• Filed: 03/28/1995
• Issued: 12/03/1996
• Est. Priority Date: 03/28/1994
• Status: Expired due to Fees

• Current Assignee: Laboratoires D'Hygiene Et De Dietetique
• Original Assignee: Laboratoires D'Hygiene Et De Dietetique
• Inventors: Liorzou, Laurent, Mikler, Claude, Dhuique-Mayer, Daniel
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/413,216
• Time in Patent Office: 616 Days
• Field of Search: 424/448, 424/449, 514/946, 514/947
• 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
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

This invention is concerned with a new transdermal matrix system for the percutaneous administration of a hormone, said matrix system, which has a support and a self-adhesive matrix, comprising a matrix containing:

(a) 20 to 42 parts by weight of a poly(styrene-isoprene-styrene) triblock copolymer,

(b) 35 to 55 parts by weight of a tackifying resin.

(c) 5 to 25 parts by weight of a plasticizing agent selected from the group consisting of oleic alcohol, peglicol 5-oleate, propyleneglycol laurate or a polypropoxyl ether of cetyl alcohol,

(d) 5 to 15 parts by weight of at least one compound selected from the group consisting of:

crotamiton, and

N-substituted 2-pyrrolidones of formula I, ##STR1## wherein R represents a (C₁ -C₁₅)-alkyl, cyclohexyl or 2-hydroxyethyl group,

(e) 0,01 to 1 part by weight of a stabilizing agent and,

(f) 0,1 to 5 parts by weight of a hormone selected from the group consisting of oestrogen components, progestogen components and mixtures thereof.

It also relates to a method for prepararing said system.

No figure.

Claims

1. A self-adhesive transdermal matrix system for the administration of a hormone by percutaneous route, said matrix system, which has a support and a self-adhesive matrix, comprises a matrix consisting essentially of:

(a) 20 to 42 parts by weight of a poly(styrene-isoprene-styrene) triblock copolymer,

(b) 35 to 55 parts by weight of a tackifying resin.

(c) 5 to 25 parts by weight of a plasticizing agent selected from the group consisting of oleic alcohol, peglicol 5-oleate, propyleneglycol laurate or a polypropoxyl ether of cetyl alcohol,

(d) 5 to 15 parts by weight of at least one compound which promotes cutaneous permeation selected from the group consisting of;

crotamiton, and

N-substituted 2-pyrrolidones of formula I, ##STR3## wherein R represents a (C₁ -C₁₅)-alkyl, cyclohexyl or 2-hydroxyethyl group,

(e) 0,01 to 1 part by weight of antioxidant agent and,

(f) 0,1 to 5 parts by weight of a hormone selected from the group consisting of oestrogen compounds, progestogen compounds and mixtures thereof.

2. A system as claimed in claim 1 wherein the plasticizing agent is oleic alcohol.

3. A system as claimed in claim 1 wherein the plasticizing agent is peglicol 5-oleate.

4. A system as claimed in claim 1 wherein the plasticizing agent is propylene glycol laurate.

5. A system as claimed in claim 1 wherein the plasticizing agent is a polypropoxyl ether of cetyl alcohol.

6. A system as claimed in claim 1 wherein the compound which promotes cutaneous permeation is selected from the group consisting of crotamiton and N-substituted 2-pyrrolidone compounds of formula I in which the R group represents a (C₁ -C₁₅)-alkyl, cyclohexyl or 2-hydroxyethyl group.

7. A system as claimed in claim 1 wherein the poly(styrene-isoprene-styrene) triblock copolymer has a styrene content of between 14 and 50% by weight with respect to the weight of said copolymer.

8. A system as claimed in claim 1 wherein the oestrogen is 17-β

-oestradiol.

9. A system as claimed in claim 1 wherein the progestogen is norethisterone acetate.

10. A system as claimed in claim 1 wherein its matrix contains per total 100 parts by weight:

(a) 37.3 parts by weight of the poly(styrene-isoprene-styrene) triblock copolymer,

(b) 38 parts by weight of tackifying resin,

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

(d) 7 parts by weight of N-octyl-2-pyrrolidone,

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

(f) 0.5 part by weight of 17-β

-oestradiol, and

(g) 2 parts by weight of norethisterone acetate.

11. A method for preparing a transdermal matrix system as claimed in claim 1, said method comprising:

(α

) mixing the SIS polymer, stabilizing agent and tackifying resin at a temperature higher than 110°

C., then homogenizing the resulting mixture to form a first homogenous mixture;

(β

) incorporating into the first homogenous mixture the promoter(s) and the plasticizer at a temperature of between 80° and

110°

C. then homogenizing the resulting mixture to form a second homogeneous mixture;

(γ

) incorporating the second homogenous mixture with the hormone selected from the group consisting of estrogen compounds, progestogen compounds and mixtures thereof, then homogenizing the resulting mixture to form a third homogenous mixture;

(δ

) coating the third homogenous mixture onto a temporary anti-adherent support in such manner as to obtain a coating on said support of 50 to 300 g/m² ; and

,

(ε

) transferring said coating to a final support.

12. A method for preparing a transdermal matrix system as claimed in claim 1, said method comprising:

(α

) mixing the SIS polymer, stabilizing agent and then the tackifying resin in a solvent of said SIS polymer, at a temperature lower than the boiling point temperature of said solvent, then homogenizing the resulting mixture to obtain a first homogenous mixture;

(β

) incorporating into the first homogenous mixture the promoter(s) and the plasticizer, then homogenizing the resulting mixture to form a second homogenous mixture;

(γ

) incorporating into the second homogenous mixture the hormone selected from the group consisting of estrogen compounds, progestogen compounds and mixtures thereof, then homogenizing the resulting mixture to form a third homogenous mixture;

(δ

) coating the third homogenous mixture, at room temperature, onto a temporary anti-adherent support in such manner as to obtain a coating on said support of 50 to 300 g/m², and,

(ε

) evaporating the solvent by heating said coating to a higher temperature than the boiling point temperature of said solvent, then transferring said coating to a final support.

13. A system as claimed in claim 5, wherein the plasticizing agent is a polypropoxyl ether of cetyl alcohol which contains 10 moles of propylene oxide per 1 mole of cetyl alcohol.

14. A system as claimed in claim 7, wherein the poly(styrene-isoprene-styrene) triblock copolymer has a styrene content of between 17 and 47% by weight with respect to the weight of said copolymer.

15. A method for preparing a transdermal matrix system as claimed in claim 10, said method comprising:

(α

) mixing the SIS polymer, stabilizing agent and tackifying resin at a temperature higher than 110°

C., to obtain a first homogeneous mixture;

(β

) incorporating into the first homogenous mixture the promoter(s) and the plasticizer at a temperature of between 80° and

110°

C. to obtain a second homogeneous mixture;

(γ

) incorporating the second homogenous mixture the hormone selected from the group consisting of estrogen compounds, progestogen compounds and mixtures thereof to obtain a third homogenous mixture;

(δ

) coating the third homogenous mixture onto a temporary anti-adherent support in such manner as to obtain a coating on said support of 50 to 300 g/m² ; and

,

(ε

) transferring said coating to a final support.

16. A method for preparing a transdermal matrix system as claimed in claim 10, said method comprising:

(α

) mixing the SIS polymer, stabilizing agent and then the tackifying resin in a solvent of said SIS polymer, at a temperature lower than the boiling point temperature of said solvent to obtain a first homogenous mixture;

(β

) incorporating into the first homogenous mixture the promoter(s) and the plasticizer to obtain a second homogenous mixture;

(γ

) incorporating into the second homogenous mixture the hormone selected from the group consisting of estrogen compounds, progestogen compounds and mixtures thereof to obtain a third homogenous mixture;

(δ

) coating the third homogenous mixture, at room temperature, onto a temporary anti-adherent support in such manner as to obtain a coating on said support of 50 to 300 g/m², and,

(ε

) evaporating the solvent by heating said coating to a higher temperature than the boiling point temperature of said solvent, then transferring said coating to a final support.