POLYMERIC MICROSPHERES PREPARED BY SPRAYING INTO COMPRESSED CARBON-DIOXIDE

Purpose. The objective was to prepare polymeric microparticles by atom izing organic polymer solutions into a spray chamber containing compre ssed CO2 (PCA-process) and to study the influence of various process p arameters on their morphological characteristics. Method. The swelling of various pharmaceutically acceptable polymers [ethyl cellulose, pol y(methyl methacrylate), poly(epsilon-caprolactone), poly(dl-lactide), poly(l-lactide) and poly(dl-lactide-glycolide) copolymers] in CO2 was investigated in order to find polymers which did not agglomerate durin g the spraying process. Poly(l-lactide) (L-PLA) microparticles were pr epared by spraying the organic polymer solution into CO2 in a speciall y designed spraying apparatus. The effect of various process (pressure and temperature of the CO2 phase, flow rate) and formulation (polymer concentration) variables on the morphology and particle size of L-PLA -microparticles was investigated. Results. Polymers with low glass tra nsition temperatures agglomerated even at low temperatures. The format ion of microparticles was favored at moderate temperatures, low polyme r concentrations, high pressures and high flow rates of CO2. High poly mer concentrations and low flow rates resulted in the formation of pol ymeric fibers. Colloidal L-PLA particles could also be prepared with t his technique in a surfactant-free environment. Initial studies on the microencapsulation of drugs resulted in low encapsulation efficiencie s. Conclusions. The PCA method is a promising technique for the prepar ation of drug-containing microparticles. Potential advantages of this method include the flexibility of preparing microparticles of differen t size and morphology, the elimination of surfactants, the minimizatio n of residual organic solvents, low to moderate processing temperature s and the potential for scaleup.