Effect of Pharmaceutical Polymer Materials on the Crystal Form and Habit of Resveratrol

OBJECTIVE To explore the different crystal habits of resveratrol(RSV) induced by pharmaceutical polymer materials, and to perform a series of crystal characterisation, equilibrium solubility and apparent solubility studies, this paper investigates the effects of pharmaceutical polymer excipients on the crystal form and habit of RSV.

METHODS Using the anti solvent method, pharmaceutical polymer materials were used to induce RSV crystallization, obtaining crystals of different morphologies. The crystals were characterized by SEM, FTIR, DSC, PXRD, SCXCRD. The equilibrium solubility and apparent solubility of RSV dissolved in simulated gastric juice(pH 1.2 hydrochloric acid solution) and simulated intestinal juice(pH 6.8 phosphate buffer solution) were also determined.

RESULTS Three different crystal habits of RSV were obtained, namely flake(RSV-P), needle(RSV-N), and columnar(RSV-C). SCXRD and PXRD results indicated that all three crystal habits belong to the same space group and crystalline form. FTIR results confirmed the structural stability and consistency across the three crystal habits. DSC results showed that minor differences in melting endothermic peaks and enthalpy values were related to the habit and size of the three crystal habits. Equilibrium solubility studies demonstrated that the equilibrium solubility of RSV-C in simulated intestinal fluid was significantly higher than that of RSV-P and RSV-N, being 1.38 and 1.08 times higher, respectively.

CONCLUSION  The BFDH model theory is employed to calculate the crystal morphology. Compared with the simulated initial morphology, pharmaceutical polymer materials exhibit a certain effect on the crystal volume and size, which is primarily attributed to the intermolecular forces between the polymer materials and the active pharmaceutical ingredient(API), as well as the structural characteristics of the polymers. This further demonstrates that rational selection of pharmaceutical polymer excipients can effectively regulate the crystal habit of drugs. Equilibrium solubility and apparent solubility results indicate that columnar RSV-C exhibits higher solubility in simulated intestinal fluid than flake RSV-P and needle RSV-N. Given that RSV is absorbed in the small intestine, the columnar crystal habit represents the most favourable among the three crystal habits.