Uncovering crystal growth and regeneration mechanism to control crystal morphology: The case study of aceclofenac

Abstract

The study of crystal growth and regeneration mechanisms is of great significance for controlling the morphology of crystals. Through the investigation of the recovery and regrowth processes of crystals, we have revealed the regeneration mechanism of aceclofenac (ACF) crystals and the influence of hydroxypropyl methylcellulose (HPMC) on the regeneration of ACF crystals. Firstly, ACF crystal regeneration experiments were conducted in acetone (ACT) and methyl acetate (MA), and it was found that the broken crystals could be successfully regenerated and restored to their original morphology, the regenerated ACF crystals in MA exhibited a larger aspect ratio. Secondly, the crystals obtained from the two solvents were placed in different solvents for regrowth, and it was shown that solvent was a key factor influencing the aspect ratio of ACF crystals. Additionally, HPMC was used to regulate the crystal morphology, it was found that the best effect was achieved when the mass fraction of HPMC was 0.5%, resulting in a regenerated crystal with an aspect ratio of only 2.19. Molecular simulation results indicated that the interaction between the radial (110) crystal facet and the solvent was weaker than that with the axial (1 0 -1) crystal facet, leading to a higher radial growth rate and a larger aspect ratio of the crystal. However, after adding HPMC, the interaction between HPMC and the radial (1 1 -1) and (110) crystal facets became stronger. HPMC selectively adsorbed on these two crystal facets, ultimately resulting in crystals with a smaller aspect ratio. The research findings of this study will provide theoretical basis for solving the problem of difficult morphology control due to crystal fragmentation in the pharmaceutical industry production process.