Optimal Solvent Screening for the Crystallization of Pharmaceutical Compounds from Multisolvent Systems

Abstract

In this study, an effort has been made to predict the solid–liquid equilibrium (SLE) behavior of different solids (pharmaceuticals) in many common solvents and their mixtures. A modified optimization of a recent thermodynamic model, the NRTL–SAC model, was used in all stages of calculation (VLE, LLE, and SLE predictions). The batch cooling–antisolvent crystallization process was simulated for seven model molecules from the initial temperature to the final temperature and for the volume fraction of each solvent. The feasible region of temperature for each crystallization case was calculated based on the bubble-point temperature of the solvent mixture and the melting point of the model molecules. The NRTL–SAC model was used in conjunction with the optimization procedure to test the complete miscibility of solvents during each part of crystallization. After estimating the optimum solvent mixture (combination) for a specific model molecule, the results for single, binary, and ternary solvent mixtures were compared. The results obtained from the binary and ternary combinations were similar in terms of crystallization yields per mass of solvent mixture and far superior to those obtained with single solvents. The proposed algorithm demonstrates flexibility, simplicity, and accuracy in predicting the phase behavior and eventual optimal solvent screening for the crystallization of pharmaceutical components.

Solubility and solid phase studies of isomeric phenolic acids in pure solvents

“…Besides, the experimental solubilities are in general lower in 1-propanol than in 2-propanol, behavior that is also predicted by NRTL-SAC simulations. For DMF, although the average deviation was higher than in 1-propanol, it is similar to values reported by other authors in binary systems containing small and medium size drug molecules [30,33,[65][66][67]. Fig.…”

Prediction of the solubility in lipidic solvent mixture: Investigation of the modeling approach and thermodynamic analysis of solubility

“…The equilibrium solubility was determined as the value when the solubility between two consecutive samples (24 h and 48 h time difference) differed by less than 10% (Bergström et al, 2007;Mota et al, 2009a;Persson et al, 2013;Sheikholeslamzadeh et al, 2012). Same procedure was followed to measure equilibrium solubility in binary and ternary solvent blends.…”

Prediction of Solubility of Active Pharmaceutical Ingredients in Single Solvents and Their Mixtures — Solvent Screening

“…One of the main applications of the thermodynamic models is in the chemical industries which use solvent (or their mixtures) [19][20][21][22]. Two cases of the vapor-liquid equilibrium of common industrial solvent systems are discussed here.…”