Composition and methods for transdermal delivery of acid labile drugs

• US 6,024,974 A
• Filed: 05/27/1997
• Issued: 02/15/2000
• Est. Priority Date: 01/06/1995
• Status: Expired due to Term

• Current Assignee: Noven Pharmaceuticals Inc (Hisamitsu Pharmaceutical Company Incorporated)
• Original Assignee: Noven Pharmaceuticals Inc (Hisamitsu Pharmaceutical Company Incorporated)
• Inventors: Li, Chensheng
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): Williamson, Michael A.
• Application Number:
  US08/863,563
• Time in Patent Office: 994 Days
• Field of Search: 424/448, 424/486, 424/487, 514/946, 514/947, 514/772.5
• US Class Current: 424/448
• 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 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• 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 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• 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

Abstract

A transdermal composition and related method are described. Specifically, the transdermal composition is substantially free of gestodene or substantially free of isopropyl myristate and substantially free of lower alkanols and comprises: (a) a therapeutically effective amount of a pharmacologically active drug which is subject to acid catalyzed degradation; (b) a pharmaceutically acceptable carrier; and (c) a penetration enhancing effective amount of a functional derivative of a fatty acid.

Claims

1. A transdermal composition substantially free of weak organic acids, of lower alkanols and of gestodene, the composition comprising (a) a therapeutically effective amount of a pharmacologically active drug subject to acid catalyzed degradation;

(b) a pharmaceutically acceptable carrier; and

(c) a penetration enhancing amount of a functional derivative of a fatty acid, wherein said derivative is selected from the group consisting of amides, alcohols, and polyols.

2. The composition of claim 1, wherein said derivative is selected from the group consisting of oleamide and oleyl alcohol.

3. The composition of claim 2, wherein said drug is norethindrone acetate.

4. The composition of claim 3, wherein said carrier is a pressure sensitive adhesive.

5. The composition of claim 1, which further comprises a solvent.

6. The composition of claim 5, wherein said carrier is comprised of a polyacrylate, said drug is norethindrone acetate;

said penetration enhancer is selected from the group consisting of oleyl alcohol and oleamide; and

said solvent is a glycol.

7. The composition of claim 5, comprising:

3% by weight of the total composition of norethindrone acetate;

0.4 percent by weight of the total composition of estradiol;

5.0 percent by weight of the total composition of polysiloxane adhesive comprising trimethylated silica treated with dimethyl siloxane in toluene;

71.6 percent by weight of the total composition of polysiloxane adhesive comprising trimethylated silica treated with polydimethylsiloxane in toluene;

5.0 percent by weight of the total composition of polyacrylate adhesive;

6.0 percent by weight of the total composition of oleamide;

2.0 percent by weight of the total composition of dipropylene glycol;

5.0 percent by weight of the total composition of polyvinylpyrrolidone; and

2.0 percent by weight of the total composition of polyoxyethylene (2) oleyl ether.

8. The composition of claim 5, comprising:

3% by weight of the total composition of norethindrone acetate;

0.4 percent by weight of the total composition of estradiol;

5.0 percent by weight of the total composition of polysiloxane adhesive comprising trimethylated silica treated with dimethyl siloxane in toluene;

71.6 percent by weight of the total composition of polysiloxane adhesive comprising trimethylated silica treated with polydimethylsiloxane in toluene;

5.0 percent by weight of the total composition of polyacrylate adhesive;

6.0 percent by weight of the total composition of oleamide;

4.0 percent by weight of the total composition of dipropylene glycol; and

5.0 percent by weight of the total composition of polyvinylpyrrolidone.

9. The composition of claim 5, comprising:

3% by weight of the total composition of norethindrone acetate;

0.8 percent by weight of the total composition of estradiol;

71.2 percent by weight of the total composition of polysiloxane adhesive comprising trimethylated silica treated with dimethyl siloxane in toluene;

5.0 percent by weight of the total composition of polyacrylate adhesive;

6.0 percent by weight of the total composition of oleyl alcohol;

4.0 percent by weight of the total composition of polyoxyethylene (2) oleyl ether; and

10.0 percent by weight of the total composition of polyvinyl-pyrrolidone.

10. The transdermal composition of claim 1, wherein said drug is scopolomine.

11. A method of enhancing the penetration of a pharmacologically active drug comprising topically applying to a mammal a composition comprising:

(a) a therapeutically effective amount of a pharmacologically active drug which is subject to acid catalyzed degradation;

(b) a pharmaceutically acceptable carrier; and

(c) a penetration enhancing effective amount of a functional derivative of a fatty acid, wherein said derivative is selected from the group consisting of amides, alcohols, and polyols, and wherein said composition is substantially free of weak organic acids, of lower alkanols, and of gestodene.

12. The method of claim 11, wherein said drug is scopolomine.

13. A stabilized patch device for transdermal delivery of a steroid drug containing a 3-keto-4-en functional group, wherein said steroid drug is stable upon extended storage of said device, comprising an effective amount of said steroid drug and a carrier, wherein said carrier has no acid functional groups and forms no acid functional groups upon storage, and wherein said carrier is substantially free of weak organic acids, of lower alkanols, and of gestodene.

14. The stabilized patch device of claim 13, wherein said steroid drug is selected from the group consisting of sex hormones and corticosteroids.

15. The stabilized patch device of claim 14, wherein said device is a matrix patch wherein said carrier comprises a biocompatible polymeric adhesive with which said steroid drug is intimately admixed.

16. The stabilized patch device of claim 15, wherein said steroid drug is a sex hormone selected from the gourp consisting of progestins, androgens, and mixtures thereof.

17. The stabilized patch device of claim 16, wherein said sex hormone is a progestin and said progestin is a member selected from the group consisting of progesterone, ethisterone (17α

-ethinyltestosterone), medroxyprogesterone, hydroxyprogesterone, norethindrone (17α

-ethinyl-19-nortestosteron), norethindrone acetate (17α

-ethinyl-19-nortestosterone acetate), dydrogesterone (9β

, 10α

-pregna-4,6-diene-3, 20-dione), chlomadinone acetate (6-chloro-6-dehydro-17α

-acetoxyprogesterone), norgestrel (13β

-ethyl-17α

-ethinyl-17β

-hudroxygon-4-en-3-one, and esters and mixtures thereof.

18. The stabilized patch device of calim 17, wherein said progestin is norethindrone acetate.