This Small Business Innovation Research Phase I project addresses the challenge of manufacturing biodegradable polymeric micro-spheres which provide prolonged, controlled release of drugs. The gas anitisolvent precipitation technique, which uses near- or supercritical carbon dioxide as an antisolvent to rapidly co-precipitate drugs from solutions in organic solvents, will be used in conjunction with hydrophobic ion pairing to manufacture micro-spheres in the correct size range for pulmonary or subcutaneous administration. Research objectives include understanding the mechanism by which particles are formed, scaling our current bench top process by 50x while maintaining desired particle size distributions, and improving particle collection schemes. Research will use both experimental and theoretical approaches to predict scaleup parameters and identify process bottlenecks. Potential commercial applications of this technology include inhalable controlled release preparations for ipratropium, a common therapeutic agent for the treatment of chronic obstructive pulmonary disease, and a subcutaneous depot formulation for isoniazid, a therapeutic agent effective for tuberculosis prophylaxis
