药用高分子辅料对白藜芦醇晶型和晶习的研究

Study on the crystal form and crystal habit of resveratrol using pharmaceutical polymer materials

关键词:  白藜芦醇  药用高分子辅料  晶习  晶型  BFDH模型

Key words:  resveratrol  pharmaceutical polymer materials  crystal habit  crystal form  BFDH model

摘要:

目的 本研究通过药用高分子辅料诱导白藜芦醇形成不同晶习，并进行一系列的晶体表征、平衡溶解度和表观溶解度的测试。方法 采用反溶剂法利用不同的药用高分子辅料诱导RSV进行结晶，得到了晶型相同而形貌不同的晶体。通过扫描电镜、红外光谱、差示扫描量热、X-射线粉末衍射对晶体进行表征。并测定不同晶习RSV在模拟胃液(pH=1.2盐酸溶液)、模拟肠液(pH=6.8磷酸盐缓冲溶液)中溶解的平衡溶解度和表观溶解度。结果 得到了三种不同晶习的RSV，分别为片状(RSV-P)、针状(RSV-N)柱状(RSV-C)。结论 结合了BFDH模型理论计算晶体形貌，发现与模拟的晶体初始形貌相比，药用高分子辅料对晶体的体积和大小有一定的影响，主要与药物高分子辅料和原料药产生分子间的作用力以及药物高分子辅料的结构有关。平衡溶解度结果表明在模拟的人工肠液中柱状RSV-C的平衡溶解度明显优于片状RSV-P和针状RSV-N，分别是二者的1.38倍、1.08倍。

Abstract:

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. METHODS Using the anti solvent method, pharmaceutical polymer materials were used to induce RSV crystallization, obtaining crystals of different morphologies. The crystal was characterized by SEM, FTIR, DSC, PXRD, XCRD. 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). CONCLUSION The BFDH model theory was combined to calculate the crystal morphology, and it was found that the pharmaceutical polymer materials had a certain effect on the volume and size of the crystals compared with the simulated initial morphology of the crystals, which was mainly related to the intermolecular forces generated by the pharmaceutical polymer materials and APIs, as well as the structure of the pharmaceutical polymer materials. The equilibrium solubility results showed that the equilibrium solubility of columnar RSV-C in the simulated intestinal juice was significantly better than that of flake and needle, which were 1.38 and 1.08 times higher than the two, respectively.