Modeling of Griseofulvin Recrystallization Conducted in a Supercritical Antisolvent Process

Abstract

Griseofulvin, an active pharmaceutical compound, has been recrystallized using a supercritical CO2 antisolvent process: the concentric tube antisolvent reactor. The experimental results indicate that the influence of some operating parameters (molar ratio of organic solvent/CO2, initial griseofulvin concentration, temperature) is qualitatively the same as for other antisolvent processes. The modeling of this process, based on the assumptions of the continuous, mixed suspension, mixed product removal precipitator, has been developed. This modeling is satisfactory for the experimental results presented in this work. Nucleation rates values between 7.1 × 108 and 1.13 × 1015 no. s−1 m−3 and particle growth rates between 0.07 and 0.57 μm s−1 have been derived from this model. The results obtained allow confirmation of the influence of the operating parameters on the crystallization processes, especially for supersaturation influence. Activation energy for the particle growth rate has been obtained at 111 kJ mol−1, indicating a surface integration control for this parameter.