Study on Dissolution Thermodynamics and Cooling Crystallization of Rifamycin S

[Image: see text] The solubility data of rifamycin S were measured in isopropanol, butyl acetate, and their mixed solvents across the temperature range of 283.15–323.15 K by the gravimetric method. The results demonstrate that the solubility of rifamycin S increases with the increasing temperature in the two pure solvents, and in the mixed solvents, it increases first and then decreases with increasing butyl acetate content. The experimental data of rifamycin S in the mixed solvents were better correlated using the modified Apelblat equation and ideal model equation. Furthermore, the relevant thermodynamic parameters of the dissolution process were determined based on the van’t Hoff equation. The obtained dissolution enthalpy and Gibbs free energy are positive in all cases, which indicate that the dissolving process of rifamycin S is endothermic and nonspontaneous. The supersolubility data of rifamycin S were measured by the laser and thermal analytic method. The results demonstrate that the width of the metastable zone of rifamycin S becomes larger with decreasing cooling rate and increasing butyl acetate content. Furthermore, the crystallization process of rifamycin S was optimized on the basis of thermodynamic research. The results showed that when V(butyl acetate):V(mixed solvent) was 0.04, the cooling rate was 0.1 K/min, the stirring rate was 150 rpm, the final crystallization temperature was 283.15 K, and the aging time was 8 h, the purity of rifamycin S crystals could reach 98.5%, and the crystalline yield was 89.6%. After crystallization optimization, the size of rifamycin S crystals increased, and the dissolution in water was improved.