It is accepted that the asymmetric growth of α-resorcinol is an intrinsic property and the solvent only plays a secondary role. Therefore, this work combines single-crystal growth experiments and molecular dynamics simulations to quantify the non-negligible modulation role of the solvent in the asymmetric growth of α-resorcinol. According to the experimental results, the growth rate ratio of α-resorcinol in water is the largest, followed by that in ethyl acetate, and ethanol had the least influence. The (01̅ 1̅ ) face along the polar −c axis is a hydroxyl-rich surface, and the capability of hydrogen bond formation determines the magnitude of the growth rate. However, the (011) face along the polar +c axis is a hydrogen-rich surface, and the growth rate mainly depends on the molecular structure of the crystalline surface and the steric hindrance between molecules. In general, the molecular arrangement of α-resorcinol along both ends of the polar c-axis makes the solvent exhibit significant modulation differences in the asymmetric growth, which are entirely attributed to the mechanisms of solvent action on the specific crystalline surface. This work will further enrich the asymmetric growth mechanism of α-resorcinol in solution and potentially provide some guidance for the selection of the solvent for other organic polar crystals.

Some polycrystalline drugs are subject to concomitant polymorphism during the manufacturing process, resulting in large batch-to-batch variation and reduced drug bioavailability. Most existing studies on concomitant polymorphism have focused only on differences in nucleation kinetics and lacked analysis of the role of growth processes in polymorph control. Herein, we conducted a systematic study on the concomitant crystallization of aripiprazole Form III and Form V under the influence of thermodynamic and kinetic factors employing thermal analysis with the Ostwald ratio as a medium. It shows that the nucleation and growth rates of both forms cross over with increasing supersaturation. The comparison between the polymorph composition computed by the Ostwald ratio and the experiments highlights the considerable influence of crystal growth on the formation of concomitant polymorphism. The effect of crystal growth at lower supersaturation is indeed minimal due to the large difference in nucleation rates, but as the supersaturation increases, the difference in nucleation rates becomes smaller and the growth rate ratio gradually becomes a key factor. The images plotted with initial concentration and crystallization temperature further demonstrate that the introduction of actual nonlinear growth kinetics can lead to improved computation accuracy of the Ostwald ratio. This work provides evidence for the application of the Ostwald ratio in the design of batch crystallization for a concomitant system.