Compositions and methods for transdermal oxybutynin therapy

• US 20030147926A1
• Filed: 11/01/2002
• Published: 08/07/2003
• Est. Priority Date: 04/26/2000
• Status: Active Grant

• Current Assignee: Allergan Sales LLC (Abbvie Incorporated)
• Original Assignee: Watson Pharmaceuticals, Inc. (Abbvie Incorporated)
• Inventors: Sanders, Steven W., Ebert, Charles D.
• Granted Patent: US 7,029,694 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61F 2013/00646 Medication patches, e.g. transcutaneous
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• 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 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• 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 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides compositions and methods for administering oxybutynin while minimizing the incidence and or severity of adverse drug experiences associated with oxybutynin therapy. In one aspect, these compositions and methods provide a lower plasma concentration of oxybutynin metabolites, such as N-desethyloxybutynin, which is presumed to be contributing at least in part to some of the adverse drug experiences, while maintaining sufficient oxybutynin plasma concentration to benefit a subject with oxybutynin therapy. The invention also provides isomers of oxybutynin and its metabolites that meet these characteristics of minimized incidence and/or severity of adverse drug experiences, and maintenance of beneficial and effective therapy for overactive bladder. In some aspects, the composition may be presented in the form of an unoccluded or free form topically administered gel.

Claims

1. An oxybutynin gel formulation for topical application comprising:

a therapeutically effective amount of oxybutynin; and

a gel carrier,

wherein the formulation has a pH of from about 4 to about 11 and wherein the oxybutynin is present as an oxybutynin free base, a pharmaceutically acceptable oxybutynin salt, or a mixture thereof, and wherein the formulation is prepared for unoccluded topical application to a skin surface.

2. The oxybutynin gel formulation of claim 1, wherein the pH of the formulation is from about 4 to about 11.

3. The oxybutynin gel formulation of claim 1, wherein the pH of the formulation is from about 5 to about 11.

4. The oxybutynin gel formulation of claim 1, wherein the pH of the formulation is from about 6 to about 11.

5. The oxybutynin gel formulation of claim 1, wherein the pH of the formulation is from about 4 to about 10.

6. The oxybutynin gel formulation of claim 1, wherein the pH of the formulation is from about 5 to about 10.

7. The oxybutynin gel formulation of claim 1, wherein the pH of the formulation is from about 6 to about 10.

8. The oxybutynin gel formulation of claim 1, wherein the pH of the formulation is about 6.

9. The oxybutynin gel formulation of claim 1, wherein the pH of the formulation is about 9.

10. The oxybutynin gel formulation of claim 1, wherein the oxybutynin is oxybutynin free base.

11. The oxybutynin gel formulation of claim 1, wherein the oxybutynin is oxybutynin chloride.

12. The oxybutynin gel formulation of claim 1, wherein the oxybutynin is a combination of oxybutynin free base and oxybutynin chloride.

13. An oxybutynin gel formulation for topical administration comprising:

a therapeutically effective amount of oxybutynin in a gel carrier, which upon unoccluded topical administration, is sufficient to provide an oxybutynin skin permeation rate of at least about 10 ug/cm² over a period of at least about 24 hours.

14. The oxybutynin gel formulation of claim 13, wherein the skin permeation rate is at least about 20 ug/cm² over a period of at least about 24 hours.

15. The oxybutynin gel formulation of claim 13, wherein the formulation has a pH that enhances oxybutynin skin permeation upon unoccluded topical administration of the formulation to the skin.

16. The oxybutynin gel formulation of claim 13, wherein the formulation includes a permeation enhancer.

17. The oxybutynin gel formulation of claim 13, wherein the oxybutynin is oxybutynin free base.

18. The oxybutynin gel formulation of claim 13, wherein the oxybutynin is oxybutynin chloride.

19. The oxybutynin gel formulation of claim 13, wherein the oxybutynin is a mixture of oxybutynin free base and oxybutynin chloride.