Transdermal Pharmaceutical Compositions Comprising Active Agents

• US 20110098258A1
• Filed: 10/26/2010
• Published: 04/28/2011
• Est. Priority Date: 10/27/2009
• Status: Active Grant

• Current Assignee: Besins Healthcare Luxemborg SARL (Besins Healthcare, Inc.)
• Original Assignee: Besins Healthcare Luxemborg SARL (Besins Healthcare, Inc.)
• Inventors: Masini-Eteve, Valerie, Canet, Denis
• Granted Patent: US 10,080,760 B2
• Time in Patent Office: Days
• US Class Current: 514/170
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/566 having an oxo group in position 17, e.g. estrone
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• 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 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

The present invention provides compositions and methods for providing sustained release of an active agent through the skin of a subject, wherein a pharmaceutical percutaneous composition comprises at least one fatty acid ester and a therapeutically effective amount of active agent.

Claims

1. A sustained release pharmaceutical composition for topical administration to a skin surface comprising:

a pharmaceutically active agent comprising one or more steroids,

a fatty acid ester,

water,

a C2-C6 monoalcohol and

a fatty acid,

wherein the weight;

weight ratio of the fatty acid ester in the composition to the total active agent in said composition is at least 4;

1 fatty acid ester;

active agent.

2. The composition of claim 1, further comprising a co-solvent.

3. The composition according to claim 1, wherein the co-solvent is present in an amount ranging from 0.01% to 7% by weight of the total weight of the pharmaceutical composition.

4. The composition according to claim 1, wherein the fatty acid ester is selected from the group consisting of ethyl oleate, isopropyl oleate, isopropyl myristate, isopropyl isostearate, isopropyl palmitate, ethyl octanoate, ethyl dodecanoate, ethyl linoleate, ethyl palmitoleate, ethyl isostearate and ethyl linolenate.

5. The composition according to claim 1, wherein the fatty acid ester is isopropyl myristate.

6. The composition according to claim 1, wherein the fatty acid ester is ethyl oleate.

7. The composition according to claim 1, wherein the fatty acid ester is the ester that would result from the reaction of the fatty acid formulated in the composition with an alcohol.

8. The composition of according to claim 1, wherein the fatty acid ester is not the ester that would result from the reaction of the fatty acid formulated in the composition with the alcohol formulated in the composition.

9. The composition according to claim 1, wherein the fatty acid ester is present in an amount ranging from 0.01% to 5% by weight of the total weight of the pharmaceutical composition.

10. The composition according to claim 1, wherein the fatty acid is a C8-C22 fatty acid selected from the group consisting of capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, isostearic acid, palmitoleic acid, linoleic acid and linolenic acid.

11. The composition according to claim 1, wherein the fatty acid is present in an amount ranging from 0.01% to 5% by weight of the total weight of the pharmaceutical composition,.

12. The composition according to claim 1, comprising 2% ethyl oleate as the fatty acid ester, 2% oleic acid as the fatty acid, and 5% propylene glycol as the co-solvent, all by weight of the total weight of the pharmaceutical composition.

13. The composition according to claim 1, comprising 0.3% ethyl oleate as the fatty acid ester, 0.3% oleic acid as the fatty acid, and 0.75% propylene glycol as the co-solvent, all by weight of the total weight of the pharmaceutical composition.

14. The composition according to claim 1, wherein the pharmaceutically active agent comprises one or more steroids selected from the group consisting of estrogens, anti-estrogens (or SERMs), androgens, anti-androgens, and progestins.

15. The composition according to claim 1, wherein the pharmaceutically active agent is selected from one or more of estradiol and progesterone, and the fatty acid ester is ethyl oleate.

16. The composition according to claim 1, wherein the pharmaceutically active agent is selected from one or more of testosterone and dihydrotestosterone (DHT), and the fatty acid ester is selected from ethyl oleate and isopropyl myristate.

17. The composition according to claim 1, wherein the active agent is present in an amount ranging from 0.01% to 5% by weight of the total weight of the pharmaceutical composition.

18. The composition according to claim 1, wherein the alcohol is selected from the group consisting of ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, and mixtures thereof.

19. The composition according to claim 1, wherein the alcohol is present in an amount ranging from 10% to 90% by weight of the total weight of the pharmaceutical composition.

20. A method for providing a sustained release of a pharmaceutically active agent through the skin of a subject, comprising topically administering to the skin of the subject a pharmaceutical composition comprising

a pharmaceutically active agent comprising one or more steroids,

a fatty acid ester,

water,

a C2-C6 monoalcohol and

a fatty acid,

wherein the weight:

weight ratio of the fatty acid ester in the composition to the total active agent in said composition is at least 4;

1 fatty acid ester;

active agent.

21. The method according claim 20, wherein the fatty acid ester is present in an amount ranging from 0.1% to 20% by weight of the total weight of the pharmaceutical composition.

22. The method according to claim 20, wherein sustained release of the pharmaceutically active agent through the skin is observed at least 24 hours after said administering.