A Review on Property Estimation Methods and Computational Schemes for Rational Solvent Design: A Focus on Pharmaceuticals

This paper provides a review of the available literature on computational schemes for rational solvent design, with a focus on solvent extraction and crystallization (the two most common unit operations) in pharmaceutical industry. The computer-aided design of solvents is important as a cost-effective tool, especially with the regular development of new pharmaceutical molecules. Also, there is a need to minimize the amount and the number of solvents used with regard to environmental, health, and toxicological concerns. This review covers the properties of interest and the predictive methods for estimation of these properties in solvent design including the group contribution based methods, quantitative structure property prediction methods and molecular modeling methods. In addition, the various optimization approaches for rational solvent design such as outer approximation, branch and bound, simulated annealing, and genetic algorithm are also discussed.