Precipitation of poly( l-lactic acid) and composite poly( l-lactic acid)-pyrene particles by rapid expansion of supercritical solutions

Abstract

The rapid expansion of supercritical solutions (RESS) was explored as a novel route to the formation of microparticles and microspheres useful in controlled drug-delivery applications. Poly( l-lactic acid) was dissolved in supercritical CO 2 with CHClF 2 as a cosolvent and precipitated by RESS. The polymer's solubility and its molecular weight in solution were found to depend on processing time because of sample polydispersity. The morphology of the precipitate (microparticles, microspheres, agglomerates, or dendrites) was examined as a function of the type of the expansion device (orifices or capillaries), preexpansion temperature, and solvent composition. Dendrites were the most common morphology when using orifices. Microsphere formation using capillaries occurred with low preexpansion temperatures and low length-to-diameter ratios. A one-dimensional fluid mechanical model of the solvent's expansion in a capillary indicates that microspheres were formed preferentially when the fluid's exit density was high, suggesting that substantial precipitation occurred outside the capillary. In the first comprehensive study of the effects of process conditions on the composite powders formed by RESS coprecipitation, pyrene (a non-polymeric fluorescent solute) was coprecipitated with poly( l-lactic acid) from supercritical CO 2-CHClF 2 solutions. Fluorescence and transmission microscopy allowed the observation of pyrene in the coprecipitate. These experiments showed clearly the uniform incorporation of pyrene microparticles within polymer microspheres, and thus, the feasibility of RESS as a technique for the coprecipitation of composite particles with multiple substances.