Phase Diagram Determination and Process Development for Continuous Antisolvent Crystallizations

Abstract

The development of an antisolvent crystallization process requires the construction of an accurate phase diagram for this ternary system of compound, solvent and antisolvent, preferably as a function of temperature. This study gives an efficient methodology to systematically determine such antisolvent phase diagrams, exemplified with four model compounds: Sodium bromate, DL-Asparagine Monohydrate, Mefenamic acid and Lovastatin. Using clear point temperature measurements, single solvent and mixed solvent-antisolvent solubilities are obtained, showing strongly non-linear solubility dependencies as well as more complex solubility behaviour as a function of antisolvent fraction. A semi-empirical model equation is used to describe the phase diagram of the antisolvent crystallization system as a function of both temperature and antisolvent fraction. The phase diagram model then allows for the identification of condition ranges for optimal productivity, yield, and suspension density in continuous antisolvent crystallization processes.

Process Design Framework for Inorganic Salt Recovery Using Antisolvent Crystallization (ASC)

“…During the ASC process, adding pure antisolvent (mass fraction of antisolvent w as on total water + antisolvent basis) to the aqueous salt solution exhibits two effects: 27 (i) the antisolvent decreases the equilibrium salt solubility C sat,s (g/g solution) in the mixed system and (ii) the overall volume of the mixed solution increases, diluting the dissolved salt (from an initial salt concentration, C F,s g/g solution, to a lower concentration, C o,s g/g solution). For the ASC process to be feasible, the decrease in solubility must be substantially higher than the equivalent salt dilution.…”

Nucleation and Growth Kinetics of Sodium Chloride Crystallization from Water and Deuterium Oxide

“…We measured the induction time distribution at each chosen supersaturation at two different sample scales, 1 g and 3 g of solvent, in Crystal16 and Crystalline, respectively, for both solvents, H 2 O and D 2 O. Measurements were performed for a range of supersaturations, which were obtained by varying the solute concentration C, as shown in Table 1. The solubility C * (T) at the experimental temperature of T exp = 25 • C was determined as 0.3599 g Solute /g Solvent for H 2 O and 0.3071 g Solute /g Solvent for and D 2 O from Van't Hoff fittings of the measured clear points [35,36]. Sample preparation and initial dissolution at 70 • C were identical to the solubility/metastable zone experiments above.…”