Solid pharmaceutical dispersions with enhanced bioavailability

Abstract

Spray dried solid dispersions comprising a sparingly soluble drug and hydroxypropylmethylcellulose acetate succinate (HPMCAS) provide increased aqueous solubility and/or bioavailability in a use environment.

1 . A process for making a solid dispersion comprising a sparingly water-soluble drug and hydroxypropyl methyl cellulose acetate succinate (HPMCAS), said process comprising the steps of:
 (a) providing a solution comprising a sparingly water-soluble drug, HPMCAS, and a solvent, said solution having a weight ratio of said drug to said HPMCAS of from 1 to 0.4 to 1 to 20;   (b) breaking up said solution into small droplets;   (c) directing said droplets and a drying gas into a drying chamber to cause evaporation of a sufficient amount of said solvent from said droplets to cause solidification of said droplets.   
     
     
         2 . The process of  claim 1 , wherein said sparingly water-soluble drug and said HPMCAS are mutually soluble in said solvent. 
     
     
         3 . The process of  claim 1 , wherein said solvent is a mixture of compounds. 
     
     
         4 . The process of  claim 1 , wherein said solvent is selected from one or more of methanol, ethanol, n-propanol, iso-propanol, butanol, acetone, methyl ethyl ketone, methyl iso-butyl ketone, ethyl acetate, propylacetate, acetonitrile, methylene chloride, toluene, 1,1,1-trichloroethane, dimethylacetamide, dimethylsulfoxide, and water. 
     
     
         5 . The process of  claim 1 , wherein said droplets solidify in less than 5 seconds to form said solid dispersion. 
     
     
         6 . A method of increasing the bioavailability of a sparingly water-soluble drug, comprising administering a composition comprising a spray-dried solid dispersion comprising said drug and hydroxypropyl methylcellulose acetate succinate (HPMCAS) to an animal, including humans, wherein said dispersion has a drug:HPMCAS weight ratio between 1:0.4 and 1:20. 
     
     
         7 . The method of  claim 6 , wherein said dispersion provides a concentration of said sparingly water-soluble drug in a use environment that is higher by a factor of at least 1.5 relative to a composition comprising an equivalent quantity of undispersed drug. 
     
     
         8 . A spray-dried solid dispersion comprising a sparingly water-soluble drug and hydroxypropyl methylcellulose acetate succinate (HPMCAS), said dispersion having a drug:HPMCAS weight ratio between 1:0.4 and 1:20. 
     
     
         9 . The solid dispersion of  claim 8 , wherein said dispersion is a homogeneous solid solution. 
     
     
         10 . The solid dispersion of  claim 9 , wherein said drug comprises amorphous drug molecularly dispersed in said dispersion. 
     
     
         11 . The spray dried solid dispersion of  claim 8 , in the form of particles less than 100 μm in diameter. 
     
     
         12 . The spray dried solid dispersion of  claim 8 , wherein said dispersion comprises spray dried particles that are solidified in less than 2 seconds.