Enhancement of Crystallization Process of the Organic Pharmaceutical Molecules through High Pressure

The enhancement of the crystallization process through high pressures was studied by using ribavirin (RVB) as a model compound. The effects of high pressure on crystallization thermodynamics, nucleation kinetics, and process yield were evaluated and discussed. The solubility of ribavirin in three pure solvents was measured at different pressures from 283.15 to 323.15 K. The results indicate that the solubility data of ribavirin decreased slightly when pressure was increased. The induction time of the cooling crystallization of ribavirin under different pressures was measured. The results show that high pressure could significantly reduce the nucleation induction period. Furthermore, the nucleation kinetic parameters under different pressures were calculated according to the classical nucleation theory. The effect of high pressure on the anti-solvent crystallization of ribavirin was also studied.