Transdermal delivery of hormones without the need of penetration enhancers
View Patent ↗The present invention relates to a patch comprising a drug-containing layer with low content of hormones, such as gestodene, and optionally an estrogen (e.g. ethinyl estradiol). Upon administering the patch to a woman, plasma levels of at least 1.0 ng/ml of Gestodene is achieved at steady state conditions without the need of incorporating penetration enhancers or permeation enhancers in the drug-containing layer. Satisfactorily plasma levels of the hormones is also achieved throughout a period of at least 1 week, making the patch applicable for being used in female contraception with the concept of administering the patch ones weekly.
1. A composition for transdermal delivery comprising a drug-containing layer wherein the drug-containing layer consists essentially of Gestodene or an ester thereof, ethinyl estradiol and at least one pharmaceutically acceptable earner which comprises a polyisobutylene polymer, one or more tackifiers selected from the group consisting of hydrocarbon resins, rosin resins and terpene resins and optionally a polybutene polymer, and wherein the drug-containing layer contains 25% to 99% by weight of polyisobutylene polymer(s) including at least one polyisobutylene polymer with a high molecular weight of about 500,000 to 2,000,000 Da and at least one polyisobutylene polymer with a low molecular weight of about 20,000 to 100,000 Da, wherein the drug-containing layer has a solubility for said Gestodene or an ester thereof of no more than 3% by weight of the drug-containing layer and the Gestodene or an ester thereof is completely dissolved in the layer, wherein the Gestodene or an ester thereof is in an amount ranging between 0.5 and 3% by weight of the drug-containing layer, and wherein the drug-containing layer excludes a skin penetration enhancer.
2. The composition according to claim 1 , wherein the tackifier is a rosin ester.
3. The composition according to claim 1 , wherein the drug-containing layer is transparent.
4. A kit comprising 1 to 11 dosage units intended for a treatment period of 12 weeks formulated in a form for transdermal delivery of Gestodene or an ester thereof, said dosage unit comprises a composition as defined in claim 1 .
5. The kit according to claim 4 , wherein the kit is intended for a treatment period of 12 weeks and the kit comprises 9 dosage units.
6. The kit according to claim 4 , wherein the kit is intended for a treatment period of 4 weeks and the kit comprises 4 dosage units.
7. The kit according to claim 4 , wherein the gestodene is present in an effective dose corresponding to a dose selected from a 6-day dose, 7-day dose, S day-dose, 14-day dose or 21-day dose.
8. The kit according to claim 4 , wherein each dosage unit comprises a Gestodene in a dose from about 0.5 to 5 mg.
9. A method for inhibiting ovulation in a female, comprising administering topically to the skin or the mucosa an effective amount of Gestodene or an ester thereof; in combination with ethinyl estradiol, by means of a composition of claim 1 , so that after single administration of said Gestodene or an ester thereof, a plasma concentration-time curve of Gestodene is achieved having plasma levels of Gestodene in a concentration of at least 1.0 ng/ml, as determined at steady state conditions.
10. The method according to claim 9 , wherein the plasma concentration-time curve of Gestodene achieves plasma levels of Gestodene in the range of 1 to 8 ng/ml following the first 6 days after single administration.
11. The kit according to claim 4 , wherein each dosage unit comprises a Gestodene in a dose from about 1 to 3 mg.
12. The kit according to claim 4 , wherein each dosage unit comprises a Gestodene in a dose from about 1.5 to 2.5 mg.
13. The composition according to claim 1 , wherein: the composition contains the Gestodene in the drug-containing layer in a dose of from about 1.5 to 2.5 mg; and the composition is transparent.
14. A kit for a treatment period of 28 days containing four transdermal delivery dosage units, each for a period of 7-day use wherein three of the 7-day use dosage units contain a composition according to claim 13 and the fourth 7-day dosage unit contains a composition with no Gestodene.
15. The composition of claim 13 , wherein the drug-containing layer comprises a rosin ester tackifier.
16. The kit of claim 14 , wherein the drug-containing layer comprises a rosin ester tackifier.
17. The kit of claim 14 , wherein the transdermal dosage units are transparent.
18. The kit of claim 14 , wherein the three dosage units with the Gestodene-containing composition comprise a hacking layer, a drug-containing layer with contains the Gestodene-containing composition and a removable release liner.
19. The kit of claim 18 , wherein the transdermal dosage units are transparent.
20. The kit of claim 18 , wherein the drag-containing layer of the transdermal dosage units have a size of 5 to 20 cm 2 .
21. The kit of claim 19 , wherein the drug-containing layer of the transdermal dosage units have a size of 5 to 20 cm 2 .
22. The composition of claim 1 , wherein the drug-containing layer contains 25% to 85% by weight of polyisobutylene polymer(s),