Compositions for delivery of insoluble agents

Abstract

Compositions and methods of making the same for improving the bioavailability of a substantially water-insoluble pharmacologically active agent are described. The composition includes a substantially water-insoluble pharmacologically active agent, and a substantially water-insoluble matrix forming material comprising enzyme digestible or bile soluble nutrients, wherein the substantially water-insoluble pharmacologically active agent is dispersed in a solid matrix and wherein said pharmacologically active agent in said matrix is substantially free of the original crystalline form.

1 . A solid composition for improving the bioavailability of a substantially water-insoluble pharmacologically active agent comprising: (1) a substantially water-insoluble pharmacologically active agent, and (2) a substantially water-insoluble matrix forming material comprising enzyme digestible or bile soluble nutrients wherein the substantially water-insoluble pharmacologically active agent is dispersed in a solid matrix and wherein said pharmacologically active agent in said matrix is substantially free of the original crystalline form. 
     
     
         2 . The composition of  claim 1 , wherein said composition has particle size less than about 500 micron in diameter. 
     
     
         3 . The composition of  claim 1 , wherein said composition has particle size less than about 200 micron in diameter. 
     
     
         4 . A solid composition comprising: (1) a substantially water-insoluble pharmacologically active agent, and (2) a substantially water-insoluble matrix forming material comprising enzyme digestible or bile soluble nutrients wherein the substantially water-insoluble pharmacologically active agent is dispersed in a solid matrix and wherein said pharmacologically active agent in said matrix is substantially free of the original crystalline form and wherein the composition has particle size less than about 500 micron in diameter. 
     
     
         5 . The composition of  claim 1 , wherein said composition is in the form of a powder, granule or pellet. 
     
     
         6 . The composition of  claim 1 , wherein said composition is filled into capsules or compressed into tablets, optionally containing other capsule or tablet excipients. 
     
     
         7 . The composition of  claim 1 , wherein said composition is formulated for oral, topical, inhalation or transmucosal drug delivery. 
     
     
         8 . The composition of  claim 1 , wherein said nutrients comprise substantially water-insoluble zein, casein, whey, collagen, gelatin, lecithin of high melting point, alpha-tocopherol semi-ester derivatives, amino acids, cellulose, or combinations thereof. 
     
     
         9 . The composition of  claim 8 , wherein the alpha-tocopherol derivative comprises a compound of formula I, its salts or solvates, 
       
         
           
           
               
               
           
         
         wherein n=0-7. 
       
     
     
         10 . The composition of  claim 9 , wherein the alpha-tocopherol derivative comprises alpha-tocopheryl succinate, its salts or solvates. 
     
     
         11 . The composition of  claim 1 , wherein said matrix forming material is a combination of zein and alpha-tocopheryl succinate, its salts or solvates at a weight ratio in the range of 1:99 to 99:1. 
     
     
         12 . The composition of  claim 1 , wherein said matrix forming material comprises in the range of 20% to 99% by weight of the composition. 
     
     
         13 . The composition of  claim 1 , wherein the composition exhibits faster dissolution in an aqueous medium, relative to the water-insoluble pharmacologically active agent in the absence of said matrix forming material. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . A process for preparing a solid composition for improving the bioavailability of a substantially water-insoluble pharmacologically active agent, said process comprising
 (a) dissolving the substantially water-insoluble pharmacologically active agent or salt or solvate thereof and a substantially water-insoluble matrix forming material comprising enzyme digestible or bile soluble nutrients in at least one or more solvents; and   (b) removing said solvent(s) under suitable conditions.   
     
     
         19 . The process of  claim 18 , wherein step (b) is carried out by vacuum drying, freeze-drying, air drying or spray drying. 
     
     
         20 . The process of  claim 18 , further comprising pulverizing, ball-milling, comminuting or jet milling to form a free-flowing, compressible and non-hydroscopic powder wherein step (b) is carried out to form particles of size in less than 500 micron in diameter.