Sustained-release composition including amorphous polymer

A method for producing a biocompatible polymer particle for sustained release of a pharmaceutical substance, wherein said particle comprises substantially amorphous biocompatible polymer having a crystallinity of no more than about 25%, and wherein said particle comprises a substantially homogeneous mixture of said pharmaceutical substance and said amorphous polymer;

• comprising the steps of:
• a) providing:
• i) a solvent,
• ii) a pharmaceutical substance,
• iii) an amphiphilic material, selected from the group consisting of sulfates, sulfonates, phosphates, phospholipids, carboxylates, sulfosuccinates, arginine esters, cholesterol esters, carbamates, carbonates and ketals,
• iv) at least one biocompatible polymer selected from the group consisting of poly(L-lactic) acid, poly(D-lactic) acid, polyglycolic acid, polyanhydride, polycarboxyphenoxyhexane, polybutyrate, and cellulose;
• and
• v) an antisolvent fluid, wherein said antisolvent fluid comprises at least one antisolvent selected from the group consisting of carbon dioxide, nitrous oxide, ethane ethylene, chlorotrifluoromethane, monofluoromethane, acetylene, 1,1-difluoroethylene, hexafluoroethane, chlorotrifluorosilane and xenon;
• b) combining said solvent, pharmaceutical substance and amphiphilic material to form a solution, wherein said pharmaceutical substance and amphiphilic material form a hydrophobic ion paired complex within said solution;
• and
• c) contacting at subcritical conditions said solution, said polymer, and said antisolvent fluid by concurrent flow to produce a mixture, wherein said mixture has a reduced temperature in the range of about 0.75-0.995, and wherein a reduced pressure relative to the antisolvent fluid is in the range of about 0.5-2.0, wherein the weight percentage of said hydrophobic ion paired complex to the total weight of said hydrophobic ion paired complex and said polymer is in the range of about 15% to 70%, and wherein the volumetric ratio of flow rate of said antisolvent fluid to the flow rate of said solution is in the range from about 5 to about 100.