Compositions and methods for preparation of poorly water soluble drugs with increased stability

Abstract

The present invention provides stable pharmaceutical compositions of poorly water soluble pharmaceutical agents and stabilizing agents which function to increase stability of the compositions. The use of stabilizing agents provide extended stability of nanoparticle suspensions and other formulations of poorly water soluble pharmaceutical agents such as docetaxel under certain conditions, for example upon dilution for administration.

1 . A composition comprising docetaxel and a stabilizing agent, wherein stability of the composition is enhanced as compared to that of a composition without the stabilizing agent. 
     
     
         2 . The composition according to  claim 1 , wherein the composition further comprises a biocompatible polymer. 
     
     
         3 . The composition according to  claim 1 , wherein the biocompatible polymer is a carrier protein. 
     
     
         4 . The composition according to  claim 3 , wherein the carrier protein is albumin. 
     
     
         5 . The composition according to  claim 4 , wherein the ratio of albumin to docetaxel is about 18:1 or less. 
     
     
         6 . The composition according to  claim 1 , wherein the composition comprises nanoparticles of docetaxel coated with a biocompatible polymer. 
     
     
         7 . The composition according to  claim 1 , wherein the biocompatible polymer is a carrier protein. 
     
     
         8 . The composition according to  claim 7 , wherein the carrier protein is albumin. 
     
     
         9 . The composition according to  claim 8 , wherein the ratio of albumin to the docetaxel is about 18:1 to less. 
     
     
         10 . The composition according to  claim 6 , wherein the nanoparticles in the composition have an average or mean particle size of no greater than about 200 nm. 
     
     
         11 . The composition according to  claim 1 , wherein the composition is a liquid suspension of docetaxel at a concentration of at least about 1 mg/mL 
     
     
         12 . The composition according to  claim 11 , wherein the composition is a liquid suspension of docetaxel at a concentration of at least about 15 mg/ml. 
     
     
         13 . The composition according to  claim 1 , wherein the composition is a dry composition that can be reconstituted to a liquid suspension with at least about 1 mg/ml docetaxel. 
     
     
         14 . The composition according to  claim 13 , wherein the dry composition is a lyophilized composition. 
     
     
         15 . The composition according to  claim 1 , wherein the stabilizing agent is a chelating agent. 
     
     
         16 . The composition according to  claim 15 , wherein the stabilizing agent is any of citrate, edentate, malic acid, pentetate, tromethamine, derivatives thereof, and mixtures thereof. 
     
     
         17 . The composition according to  claim 16 , wherein the stabilizing agent is citrate. 
     
     
         18 . The composition according to  claim 17 , wherein the composition further comprises sodium chloride. 
     
     
         19 . The composition according to  claim 18 , wherein the composition comprise about 200 mM sodium citrate and about 300 mM sodium chloride. 
     
     
         20 . The composition according  claim 1 , wherein the stabilizing agent is sodium pyrophosphate or sodium gluconate. 
     
     
         21 - 36 . (canceled)