Investigations on growth intensification of p-toluamide crystals based on growth rate analysis and molecular simulation

Abstract

Promoting crystal growth is of great practical importance in the pharmaceutical industry, especially for manufacturing large crystals. In this work, intensification of crystal growth was investigated by using p-toluamide as a model compound. The crystal habit and the functional groups of different crystal faces of p-toluamide were analyzed from the crystal structure data. The growth rate of the (100) and (011) faces of p-toluamide was systematically measured by single crystal experiments and the effect of additives on crystal growth was evaluated. It was found that different additives could selectively promote the growth of specific crystal faces. Molecular simulation was used to investigate the influence mechanism of additives on (011) crystal face growth. It was revealed that the special promotion effect is due to the fact that the additive molecules repel the solvent molecules which exhibit a stronger inhibiting effect, thus eliminating the negative influence of the solvent on the surface diffusion of p-toluamide.