Compositions and Methods for Transdermal Oxybutynin Therapy

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.

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 μg/cm 2  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 μg/cm 2  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. 
   
   
       20 - 27 . (canceled)