Kinetics of particle formation in the gas antisolvent precipitation process

An original experimental setup based on UY-vis spectroscopy was developed to study the precipitation kinetics of a biodegradable polymer by gas antisolvent processes (GAS). Poly(L-lactide) acid (PLA) precipitations were carried out in a high-pressure optical cell equipped with sapphire windows, working at 1-80 bar and 301.15-307.15 K The particle formation and precipitation kinetics were investigated in situ by measuring UY-vis absorbance of polymeric particles at a wavelength of 600 nm. They were measured in a batch system at different pressurization rates (different supersaturation conditions). To rationalize the precipitation kinetics in GAS processes, a population balance model was developed considering particle nucleation, growth, aggregation, and settling. Nucleation and growth were represented by the McCabe model, whereas both independent- and nonindependent-kernel Smoluchowski's coagulation equations were used for aggregation. Settling was approximated by a first-order kinetic. Absorbance measurements were related to the second moment of the simulated particle-size distribution, and the kinetic parameters were estimated based on spectroscopic data. The model gave a correct phenomenological representation of all experimental data and fairly predicted the particle-size distribution of the precipitated PLA microparticles.