Parametric analysis of homogeneous and heterogeneous nucleation in subcritical CO2-mediated antisolvent crystallization

Analysis of the Mechanism of Cholesterol Particle Formation by Liquid Antisolvent Crystallization

“…It is posited that the initial low change of solution turbidity corresponds to primary nucleation, while the later rapid change of turbidity is an indicator of secondary nucleation. As explained in our previous work, the secondary nucleation rates are typically higher in magnitude compared to the primary nucleation rate, which is due to “seeding” by the primary nuclei. It is based on these observations that a 2-step primary homogeneous + secondary nucleation mechanism has been proposed in the present work.…”

“…A model of the LAS process for estimating the time-dependent variations of the solid solute supersaturation, and rates of nucleation and growth of the precipitated nuclei are utilized based on our previous work. , The mathematical model primarily computes the supersaturation, nucleation rates, and average particle size so as to confirm the proposed mechanism. The following subsections present the key equations for calculating the instantaneous nucleation and growth rates for computing the particle size.…”

“…Additionally, the effect of the nature of solvents (e.g., acetone and acetonitrile) on particle size/shape due to the variation in their polarity and solubilizing capacity for cholesterol has also been investigated. In our previous work on the GAS process, 41 cholesterol microparticles were produced from the solution of acetone using subcritical carbon dioxide (CO 2 ) as an antisolvent. Accordingly, the effects of variation of the antisolvent on particle size and shape too are compared for precipitation of cholesterol by the two processes.…”

“…The solubilities of cholesterol (x 3 *) in aqueous organic solvent mixtures have been measured by the gravimetric method at various water mole fractions (x 1 ) ranging from x 1 = 0.1 to 0.75 and temperatures ranging from T = 290.5 to 299.5 K. The detailed experimental procedure is reported elsewhere by the present authors. 41 In brief, an excess amount of cholesterol was added to the binary aqueous organic solvent mixture with a predefined composition and placed in the jacketed glass vessel. The solution was continuously stirred for 24 h at the selected temperature.…”

Process intensified anti-solvent crystallization of o-aminobenzoic acid via sonication and flow

“…As supersaturation is increased with anti-solvent, homogenous nucleation might dominate and therefore the probability of nucleation increases as well [28]. Fig.…”