Nucleation and Growth Rates of Poly(l-lactic acid) Microparticles during Precipitation with a Compressed-Fluid Antisolvent

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Abstract
We measured nucleation and growth rates of poly(L-lactic acid) (PLLA) microparticles produced during precipitation with a compressed-fluid antisolvent (PCA). The injector/precipitator used in this study satisfied the constraints and assumptions incorporated in the development of the mixed-suspension, mixed-product-removal population balance theory. A semicontinuous operation mode with batch product filtering was developed, and results from product particle size distributions allowed nucleation and growth rates to be determined through the use of population balances. Kinetic data, obtained by operating the precipitator under various degrees of supersaturation and suspension density, were used to generate a nucleation rate model for PLLA. Model results indicate a relative kinetic order of 1 and a linear dependence of the nucleation rate on the suspension density. First-order dependence of the nucleation rate on suspension density suggests secondary nucleation mechanism(s) are operative within this PCA flow system and may explain the relative insensitivity of particle size distributions to changes in PCA operating conditions.