(349a) Rapid Screening of Solvents for Crystallization Using Group Contribution Method

Regardless of the technique of crystallization – cooling or anti-solvent, the choice of solvent can change the outcome of crystallization often at the same operating conditions. The changes in the intermolecular interactions between solute and solvent can either prevent the attachment of solute molecule at certain configurations or can encourage the interactions between solute-solute molecules. The specific molecular interactions can be studied with molecular simulations, but it requires compatible topology file of the solute and solvent molecules coupled with sufficient computational power. However, the complexity of the problem can be reduced by understanding contribution of each functional group on the solute and solvent molecule towards energy of solvation. Both of the crystallization techniques require the use of solvents which maintain the crystallization in a regime where desired crystal structure is obtained. The regime can be influenced by the energy of solvation. The dynamics of these solvation shell can be used to optimize the choice of solvent along with the operating conditions to optimize the process of crystallization. Technique of group contribution allow classifying specific molecular interactions based on the functional groups. For crystallization in pharmaceutical industries, the solvents must be chosen from a list of approved solvents and hence the technique of group contribution can help rapidly screen the solvents to maintain the crystallization in a desired regime based on the necessary functional groups.