Claims for Patent: 7,045,145

Summary for Patent: 7,045,145

Title:	Transdermal contraceptive delivery system and process
Abstract:	A transdermal contraceptive delivery system (TCDS) for fertility control in women is described. It comprises a backing layer, an adjoining layer of a solid absorption adhesive polymer matrix in which effective daily doses of an estrogen and a progestin are dispersed and released for transdermal absorption. Presently preferred is the use of the synthetic estrogen, ethinyl estradiol, and the synthetic progestin, levonorgestrel. Along with these two steroidal contraceptive agents, a combination of several chemical skin permeation enhancing agents, including capric acid, blended at specific weight ratios, ranging from 2:1:1:0.8 to 6:1:1:0.8, are homogeneously dispersed in the adhesive polymer matrix. The invention also provides a method of fertility control utilizing the transdermal contraceptive delivery system.
Inventor(s):	Chien; Te-Yen (Neshanic Station, NJ)
Assignee:	Agile Therapeutics, Inc. (West Conshohocken, PA)
Application Number:	10/130,913
Patent Claims:	1. A transdermal delivery system comprising a backing layer, and an adhesive polymer matrix affixed to the backing layer, wherein the adhesive polymer matrix is formulated by combining, on a weight percentage basis: a) from about 0% to about 10% of a humectant/plasticizer; b) from about 20% to about 70% of an adhesive copolymer; c) from about 10% to about 60% percent of a combination of skin permeation enhancing agents which is a mixture comprising dimethyl sulfoxide, a fatty (C.sub.8 C.sub.20) alcohol ester of lactic acid, a lower (C.sub.1 C.sub.4) alkyl ester of lactic acid and capric acid present in ratio ranging from about 2:1:1:0.8 to about 6:1:1:0.8, respectively; d) a progestin hormone; and e) an estrogen hormone. 2. The transdermal delivery system of claim 1, wherein the progestin is levonorgestrel. 3. The transdermal delivery system of claim 1, wherein the estrogen is selected from the group consisting of ethinyl estradiol and 17 .beta.-estradiol. 4. The transdermal delivery system of claim 1, wherein the humectant/plasticizer is a polyvinylpyrrolidone/vinyl acetate. 5. The transdermal delivery system of claim 4, wherein the polyvinylpyrrolidone is formulated in an amount of about 60% w/w and the vinyl acetate is formulated in an amount of about 40% w/w in the polyvinylpyrrolidone/vinyl acetate mixture. 6. The transdermal delivery system of claim 1, wherein the adhesive copolymer comprises a polyacrylate copolymer. 7. The transdermal delivery system of claim 6 wherein the polyacrylate copolymer comprises a 2-ethylhexyl acrylate monomer. 8. The transdermal delivery system of claim 7 wherein the polyacrylate copolymer further comprises about 3 to 60% w/w vinyl acetate. 9. The transdermal delivery system of claim 1 wherein the fatty alcohol ester of lactic acid is lauryl lactate. 10. The transdermal delivery system of claim 9 wherein the lower alkyl ester of lactic acid is ethyl lactate. 11. The transdermal delivery system of claim 10 wherein the dimethyl sulfoxide, lauryl lactate, ethyl lactate and capric acid are formulated in a ratio of between about 2:1:1:0.8 and 6:1:1:0.8, respectively. 12. The transdermal delivery system of claim 11 wherein the dimethyl sulfoxide, lauryl lactate, ethyl lactate and capric acid are formulated in a ratio of about 4:1:1:0.8, respectively. 13. The transdermal delivery system of claim 3, formulated for delivery of ethinyl estradiol and levonorgestrel, wherein the ethinyl estradiol is transdermally delivered at a rate of between about 10 .mu.g and 50 .mu.g per day for a term of about one day to about one week, and the levonorgestrel is transdermally delivered at a rate of at least 20 .mu.g per day for a term of about one day to about one week. 14. The transdermal delivery system of claim 13, wherein the levonorgestrel is transdermally delivered at a rate of at least 30 .mu.g per day for a term of about one day to about one week. 15. The transdermal delivery system of claim 13, wherein the levonorgestrel is transdermally delivered in an amount sufficient to produce a blood concentration of at least 1,000 pg/ml. 16. The transdermal delivery system of claim 1 wherein the adhesive polymer matrix has a cross-sectional dimension of from about 10 to 300 microns. 17. The transdermal delivery system of claim 1, wherein the adhesive polymer matrix has a maximum surface area of 12.5 cm.sup.2. 18. A method of controlling fertility by applying to the skin of a subject desiring such treatment a transdermal delivery system comprising: a backing layer, and an adhesive polymer matrix affixed to the backing layer, wherein the adhesive polymer matrix is formulated by combining, on a weight percentage basis: a) from about 0% to about 10% of a humectant/plasticizer; b) from about 20% to about 70% of an adhesive copolymer; c) from about 10% to about 60% percent of a combination of skin permeation enhancing agents which is a mixture comprising dimethyl sulfoxide, a fatty (C.sub.8 C.sub.20) alcohol ester of lactic acid, a lower (C.sub.1 C.sub.4) alkyl ester of lactic acid and capric acid present in ratio ranging from about 2:1:1:0.8 to about 6:1:1:0.8, respectively; and d) an amount of one or more fertility controlling hormones comprising a progestin and an estrogen effective to deliver at least a minimum effective daily dose of the one or more hormones to effect fertility control for between about one and about 7 days; wherein the transdermal delivery system is replaced once each week for three of four successive weeks of a menstrual cycle, for successive menstrual cycles extending as fertility control is desired. 19. The method of claim 18, wherein the transdermal delivery system delivers levonorgestrel. 20. The method of claim 19, wherein the transdermal delivery system delivers an estrogen selected from the group consisting of ethinyl estradiol and 17 .beta.-estradiol. 21. The method of claim 18, wherein the humectant/plasticizer in the transdermal delivery system is a polyvinylpyrrolidone/vinyl acetate. 22. The method of claim 21, wherein the polyvinylpyrrolidone is formulated in an amount of about 60% w/w and the vinyl acetate is formulated in an amount of about 40% w/w in the polyvinylpyrrolidone/vinyl acetate mixture. 23. The method of claim 18, wherein the adhesive copolymer in the transdermal delivery system comprises a polyacrylate copolymer. 24. The method of claim 23 wherein the polyacrylate copolymer comprises a 2-ethylhexyl acrylate monomer. 25. The method of claim 24 wherein the polyacrylate copolymer further comprises about 3 to 60% w/w vinyl acetate. 26. The method of claim 18 wherein the fatty alcohol ester of lactic acid in the transdermal delivery system is lauryl lactate. 27. The method of claim 26 wherein the lower alkyl ester of lactic acid in the transdermal delivery system is ethyl lactate. 28. The method of claim 27, wherein the dimethyl sulfoxide, lauryl lactate, ethyl lactate and capric acid in the transdermal delivery system are formulated in a ratio of between about 2:1:1:0.8 and 6:1:1:0.8, respectively. 29. The method of claim 28 wherein the dimethyl sulfoxide, lauryl lactate, ethyl lactate and capric acid in the transdermal delivery system are formulated in a ratio of about 4:1:1:0.8, respectively. 30. The method of claim 20, wherein the transdermal delivery system is formulated for delivery of ethinyl estradiol and levonorgestrel, wherein the ethinyl estradiol is transdermally delivered at a rate of between about 10 .mu.g and 50 .mu.g per day for a term of about one day to about one week, and the levonorgestrel is transdermally delivered at a rate of at least 20 .mu.g per day for a term of about one day to about one week. 31. The method of claim 30, wherein the levonorgestrel is transdermally delivered at a rate of at least 30 .mu.g per day for a term of about one day to about one week. 32. The method of claim 30, wherein the levonorgestrel is transdermally delivered in an amount sufficient to produce a blood concentration of at least 1,000 pg/ml. 33. The method of claim 18 wherein the adhesive polymer matrix in the transdermal delivery system has a cross-sectional dimension of from about 10 to 300 microns. 34. The method of claim 18, wherein the adhesive polymer matrix in the transdermal delivery system has a maximum surface area of 12.5 cm.sup.2.