The effect of solvent–crystal interaction on the morphology of a solvate of rifampicin

Abstract

The introduction of unexpected solvent is inevitable in the crystallization process of rifampicin in industry, which could lead to products with different morphologies. Therefore, the study of crystal habit is needed for preparing rifampicin with better performance. In this work, an unreported solvate of rifampicin was prepared in n-butanol/acetone solvent. The interactions among solutes were analyzed through Hirshfeld surfaces and population fingerprints. The crystal morphology of the solvate in a vacuum was predicted by employing the attachment energy (AE) model, acquiring six habit faces. Surface structures of the faces were studied. Molecular electrostatic potentials (ESPs), concentration distribution and mean squared distribution (MSD) were then used to analyze the crystal face–solvent interface. By using the modified attachment energy (MAE) model, the morphology of rifampicin in n-butanol/acetone was finally obtained through calculations. The results show that the intermolecular interactions of solvate molecules were dominantly H⋯H and H⋯O/O⋯H contacts. Six morphologically important faces were found in the solvate crystal simulated in a vacuum, and among them, the (0 −2 0), (0 2 0), (0 0 1) and (1 0 0) faces were morphologically more important. It was found that the diffusion ability, surface structure and ESP were all important to the inhibitory effect. The morphology of the solvate was largely altered in the presence of n-butanol/acetone solvent and was consistent with the experiment result.