Preparation of drug particles using evaporation precipitation into aqueous solutions

Abstract

A method for preparing poorly water soluble drug particles is disclosed. The method comprises dissolving a drug in at least one organic solvent to form a drug/organic mixture, spraying the drug/organic mixture into an aqueous solution and concurrently evaporating the organic solvent in the presence of the aqueous solution to form an aqueous dispersion of the drug particles. The resulting drug particles are in the nanometer to micrometer size range and show enhanced dissolution rates and reduced crystallinity when compared to the unprocessed drug. The present invention additionally contemplates products and processes for new drug formulations of insoluble drug particles having high dissolution rates and extremely high drug-to-excipient ratios.

What is claimed is: 
     
         1 . A composition of poorly water soluble drug particles having a drug-to-excipient ratio of greater than about 3:1; a dissolution rate greater than about 70% drug dissolved about 3 times faster than the bulk drug; and a drug potency greater than about 66%. 
     
     
         2 . The composition of  claim 1  wherein the drug particles have a surface area and wherein the surface area is greater than about 2.5 m 2 /g, 5 m 2 /g, 10 m 2 /g, 20 m 2 /g or 30 m 2 /g. 
     
     
         3 . The composition of  claim 2 , wherein the drug-to-excipient ratio is greater than about 5:1, 7:1 or 10:1. 
     
     
         4 . The composition of  claim 3 , wherein the drug potency is about 70%, 80%, 90% or 100%. 
     
     
         5 . The composition of  claim 4 , wherein the amount of drug dissolved is about 80%, 85%, 90%, 95% or 100%. 
     
     
         6 . The composition of  claim 5 , wherein the dissolution occurs about 5, 7, 10, 15, 20, 25 or 30 times faster than the bulk drug. 
     
     
         7 . The composition of  claim 6 , wherein the drug particles are produced by solution precipitation methods, anti-solvent precipitation, spray drying, spray freezing, evaporative precipitation into an aqueous solution, wet milling, mechanical milling, or lyophilization. 
     
     
         8 . The composition of  claim 7 , wherein the drug particles are amorphous, crystalline or semi-crystalline. 
     
     
         9 . A poorly water soluble drug particle composition, wherein the composition produced by evaporative precipitation into an aqueous solution and wherein said formulation having a drug-to-excipient ratio greater than about 3:1. 
     
     
         10 . The composition of  claim 9 , wherein the drug-to-excipient ratio is greater than about 5:1, 7:1 or 10:1. 
     
     
         11 . The composition of  claim 10 , wherein the drug particles have a surface area and wherein the surface area is greater than about 2.5 m 2 /g, 5 m 2 /g, 10 m 2 /g, 20 m 2 /g or 30 m 2 /g. 
     
     
         12 . The composition of  claim 11 , wherein the drug potency is about 66%, 70%, 80%, 90% or 100%. 
     
     
         13 . The composition of  claim 12 , wherein the amount of drug dissolved is about 80%, 85%, 90%, 95% or 100%. 
     
     
         14 . The composition of  claim 13 , wherein the dissolution occurs about 5, 7, 10, 15, 20, 25 or 30 times faster than the bulk drug. 
     
     
         15 . The composition of  claim 14 , wherein the drug particles are amorphous, crystalline or semi-crystalline. 
     
     
         16 . A method of producing drug formulations comprising the steps of: preparing stabilized drug particles in a suspension solution by evaporative precipitation into an aqueous solution; separating the particles from the suspension solution; and drying the resulting formulation to produce a drug formulation having a drug potency of about 66%. 
     
     
         17 . The method of  claim 16 , wherein the drug particles are separated by centrifugation, settling, or filtering. 
     
     
         18 . The method of  claim 16 , wherein the drug particles are lyophilized, vacuum dried, or spray dried. 
     
     
         19 . The method of  claim 16 , wherein the drug-to-excipient ratio is greater than about 3:1, 5:1, 7:1 or 10:1. 
     
     
         20 . The method of  claim 19 , wherein the drug particles have a surface area and wherein the surface area is greater than about 2.5 m 2 /g, 5 m 2 /g, 10 m 2 /g, 20 m 2 /g or 30 m 2 /g. 
     
     
         21 . The method of  claim 20 , wherein the drug potency is about 70%, 80%, 90% or 100%. 
     
     
         22 . The method of  claim 21 , wherein the amount of drug dissolved is about 70%, 80%, 85%, 90%, 95% or 100%. 
     
     
         23 . The method of  claim 22 , wherein the dissolution occurs about 5, 7, 10, 15, 20, 25 or 30 times faster than the bulk drug. 
     
     
         24 . The pharmaceutical composition comprising the composition of  claim 1 . 
     
     
         25 . The pharmaceutical composition comprising the composition of  claim 9 . 
     
     
         26 . The method of  claim 16 , comprising a further step of formulating the particles for pharmaceutical administration. 
     
     
         27 . The method of  claim 16 , comprising a further step of formulating the particles for pharmaceutical administration.