Compositions containing opioid antagonists

Abstract

Compositions containing opioid antagonists, particularly alvimopan and its active metabolite, with improved solubility and bioavailability for oral or parenteral administration, injectable dosage formulations, kits, and methods of making and using same are disclosed. In preferred embodiments, invention provides injectable formulations containing opioid antagonists, particularly alvimopan and its active metabolite, having low solubility that may be readily prepared, are stable during storage, and provide maximum levels of opioid antagonists when administered parenterally, particularly via injection. The results are achieved by a combination of processing techniques and component selection.

What is claimed is: 
     
         1 . An injectable dosage formulation comprising:
 a. a pharmaceutically-acceptable metal salt of the compound of Formula II:   
       
         
           
           
               
               
           
         
       
       and
 b. at least one sugar alcohol bulking agent that crystallizes;
 wherein the composition has a density of less than about 1.0 g/cm 3 ; and 
 wherein, upon administration to a patient, the composition has improved solubility and bioavailability for oral or parenteral administration. 
 
 
     
     
         2 . A composition according to  claim 1 , wherein the metal salt is sodium. 
     
     
         3 . A composition according to  claim 1 , wherein the sugar alcohol bulking agent is mannitol. 
     
     
         4 . A composition according to  claim 1 , wherein the formulation is reconstituted with an aqueous pharmaceutically acceptable solvent prior to its administration to a patient in need thereof.