Transdermal estrogen device and delivery

• US 8,231,906 B2
• Filed: 07/10/2008
• Issued: 07/31/2012
• 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): Sullivan, Daniel
• Assistant Examiner(s): FISHER, MELISSA L
• Application Number:
  US12/216,811
• Publication Number:
  US 20100008991A1
• Time in Patent Office: 1,482 Days
• Field of Search: None
• US Class Current: 424/487
• 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 monolithic transdermal drug delivery system for estradiol, comprising a single polymer matrix layer defining an active surface area and comprising a polymer matrix comprising estradiol as the only drug, wherein the polymer matrix layer has a coat weight selected from the group consisting of 12.5 mg/cm² and 15 mg/cm², includes greater than 0.156 mg/cm² estradiol, and achieves an estradiol flux that is greater than 0.01 mg/cm²/day, based on the active surface area.

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

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

4. The transdermal drug delivery system of claim 3, wherein the penetration enhancer comprises oleyl alcohol.

5. The transdermal drug delivery system of claim 3, wherein the penetration enhancer comprises dipropylene glycol.

6. The transdermal drug delivery system of claim 3, wherein the penetration enhancer comprises oleyl alcohol and dipropylene glycol.

7. The transdermal drug delivery system 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 transdermal drug delivery system of claim 1, wherein the 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 transdermal drug delivery system of claim 1, wherein the 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. A monolithic transdermal drug delivery system for estradiol comprising a single polymer matrix layer comprising estradiol as the only drug, wherein the polymer matrix layer has a coat weight selected from the group consisting of 12.5 mg/cm² and 15 mg/cm², and 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 and is effective to deliver an amount of estradiol per day of about 0.025, 0.0375, 0.05, 0.075 and 0.1 mg/day, respectively.

11. A method for administering estradiol, con to the skin or mucosa of a subject in need thereof a monolithic transdermal drug delivery system comprising a single polymer matrix layer defining an active surface area and comprising a polymer matrix comprising estradiol as the only drug, wherein the polymer matrix layer has a coat weight selected from the group consisting of 12.5 mg/cm² and 15 mg/cm², includes greater than 0.156 mg/cm² estradiol, and achieves an estradiol flux that is greater than 0.01 mg/cm²/day, based on the active surface area.

12. The method of claim 11, 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 and is effective to deliver an amount of estradiol per day of about 0.025, 0.0375, 0.05, 0.075 and 0.1 mg/day, respectively.

13. A method of making a monolithic transdermal drug delivery system for administering estradiol, comprising forming a 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 polymer matrix to a support layer to form a single polymer matrix layer such that the polymer matrix layer has a coat weight selected from the group consisting of 12.5 mg/cm² and 15 mg/cm² and includes greater than 0.156 mg/cm² estradiol.

14. The method of claim 13, 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.