Transdermal estrogen device and delivery

• US 9,730,900 B2
• Filed: 07/20/2012
• Issued: 08/15/2017
• Est. Priority Date: 07/10/2008
• Status: Active Grant

• Current Assignee: Noven Pharmaceuticals (Hisamitsu Pharmaceutical Company Incorporated)
• Original Assignee: Noven Pharmaceuticals (Hisamitsu Pharmaceutical Company Incorporated)
• Inventors: Mantelle, Juan
• Primary Examiner(s): Fisher, Melissa
• Application Number:
  US13/553,972
• Publication Number:
  US 20130156815A1
• Time in Patent Office: 1,852 Days
• Field of Search: None
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

Described are transdermal drug delivery systems for the transdermal administration of estrogen, comprising a polymer matrix and estrogen. Methods of making and using such systems also are described.

Claims

1. A method for administering estradiol, comprising applying to the skin or mucosa of a subject in need thereof a monolithic transdermal drug delivery system consisting of (i) a backing layer and (ii) a single adhesive polymer matrix layer defining an active surface area and comprising an adhesive polymer matrix comprising estradiol as the only drug, wherein the polymer matrix has a coat weight of greater than about 10 mg/cm² and includes greater than 0.156 mg/cm² estradiol, and the system achieves an estradiol flux of from about 0.0125 to about 0.05 mg/cm²/day, based on the active surface area.

2. The method of claim 1, wherein the adhesive polymer matrix comprises a polymer blend comprising an acrylic adhesive, a silicone adhesive, and soluble polyvinylpyrrolidone (PVP).

3. The method of claim 1, wherein the adhesive polymer matrix comprises about 2-25% by weight acrylic adhesive, about 45-70% by weight silicone adhesive, about 2-25% by weight soluble PVP, about 5-15% penetration enhancer, and about 0.1-10% by weight estradiol, all based on the total dry weight of the adhesive polymer matrix.

4. The method of claim 3, wherein the penetration enhancer comprises oleyl alchol.

5. The method of claim 3, wherein the penetration enhancer comprises dipropylene glycol.

6. The method of claim 3, wherein the penetration enhancer comprises oleyl alcohol and dipropylene glycol.

7. The method of claim 3, wherein the acrylic adhesive and silicone adhesive are present in a ratio of from about 1:

2 to about 1;

6, based on the total weight of the acrylic and silicone adhesives.

8. The method of claim 1, wherein the adhesive polymer matrix comprises an amount of estradiol effective to deliver a therapeutically effective amount of estradiol over a period of time selected from the group consisting of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days and at least 7 days.

9. The method of claim 1, wherein the adhesive polymer matrix comprises an amount of estradiol effective to deliver an amount of estradiol selected from the group consisting of about 0.025, 0.0375, 0.05, 0.075 and 0.1 mg/day.

10. The method of claim 1, wherein the system achieves an estradiol flux of about 0.0125 mg/cm²/day, based on the active surface area.

11. The method of claim 1, wherein the system achieves an estradiol flux of about 0.0133 mg/cm²/day, based on the active surface area.

12. The method of claim 1, wherein the system achieves an estradiol flux of about 0.015 mg/cm²/day, based on the active surface area.

13. The method of claim 1, wherein the system achieves an estradiol flux of about 0.0167 mg/cm²/day, based on the active surface area.

14. The method of claim 1, wherein the system achieves an estradiol flux of about 0.0175 mg/cm²/day, based on the active surface area.

15. The method of claim 1, wherein the adhesive polymer matrix comprises about 1.6% by weight estradiol, based on the total dry weight of the adhesive polymer matrix.

16. A method of making a monolithic transdermal drug delivery system for administering estradiol consisting of (i) a backing layer, (ii) a single adhesive polymer matrix layer and, optionally, (iii) a release liner, comprising forming an adhesive polymer matrix comprising estradiol as the only drug and a polymer blend comprising an acrylic adhesive, a silicone adhesive, and soluble PVP, and applying the adhesive polymer matrix to a support layer to form a single adhesive polymer matrix layer such that the adhesive polymer matrix layer has a coat weight of greater than about 10 mg/cm² and includes greater than 0.156 mg/cm² estradiol, wherein the system achieves an estradiol flux of from about 0.0125 to about 0.05 mg/cm²/day, based on the active surface area.

17. The method of claim 16, wherein the system has an active surface area that is about 60% of a size selected from the group consisting of 2.5, 3.75, 5.0, 7.5 and 10.0 cm².

18. The method of claim 16, wherein the system achieves an estradiol flux of about 0.0125 mg/cm²/day, based on the active surface area.

19. The method of claim 16, wherein the system achieves an estradiol flux of about 0.0133 mg/cm²/day, based on the active surface area.

20. The method of claim 16, wherein the system achieves an estradiol flux of about 0.015 mg/cm²/day, based on the active surface area.

21. The method of claim 16, wherein the system achieves an estradiol flux of about 0.0167 mg/cm²/day, based on the active surface area.

22. The method of claim 16, wherein the system achieves an estradiol flux of about 0.0175 mg/cm²/day, based on the active surface area.

23. The method of claim 16, wherein the adhesive polymer matrix comprises about 1.6% by weight estradiol, based on the total dry weight of the adhesive polymer matrix.