School of Pharmacy & School of Biological and Food Engineering, Changzhou University, Changzhou 213164, P.R., China.
School of Pharmacy & School of Biological and Food Engineering, Changzhou University, Changzhou 213164, P.R., China.
Int J Pharm. 2023 Mar 5;634:122644. doi: 10.1016/j.ijpharm.2023.122644. Epub 2023 Jan 27.
Different from previous co-amorphous systems, co-amorphous resveratrol and piperine (namely RES-PIP CM) showed much lower dissolution in comparison to the original two crystalline drugs owing to its gel formation during dissolution. The purpose of this study is to investigate the mechanism of gel formation and seek strategies to eliminate such gelation. It was found that the dissolution performance of RES-PIP CM and the properties of formed gels were significantly affected by the medium temperature and stoichiometric ratio of components. Multiple characterization results confirmed that the gelation process underwent the decrease of T caused by water plasticization, and then entered into its supercooled liquid state with high viscosity, accompanied by self-assembly of molecules. Furthermore, the study answered the question that whether such gelation of RES-PIP CM could be eliminated by porous carrier materials. The materials, mesoporous silica (MES) and attapulgite (ATT), provided barrier and well separation between molecules and particles of RES-PIP CM by the pore steric hindrance, and impeded the self-assembly and aggregation, hence achieving the degelation and dissolution improvement. The present study highlights the importance of recognizing gelation potential of some co-amorphous formulations, and provides an effective strategy to eliminate gelation in developing high quality co-amorphous drug products.
与以往的共无定形系统不同，共无定形白藜芦醇和胡椒碱（即 RES-PIP CM）在溶解过程中由于凝胶形成而表现出比原始两种晶态药物更低的溶解度。本研究的目的是探讨凝胶形成的机制，并寻求消除这种凝胶化的策略。结果发现，RES-PIP CM 的溶解性能和形成凝胶的性质受到介质温度和成分化学计量比的显著影响。多种表征结果证实，凝胶化过程经历了由水增塑引起的 T 降低，然后进入高粘度的过冷液体状态，伴随着分子的自组装。此外，该研究回答了 RES-PIP CM 这种凝胶化是否可以通过多孔载体材料消除的问题。介孔硅（MES）和凹凸棒石（ATT）等材料通过孔位空间位阻，为 RES-PIP CM 的分子和颗粒提供了障碍和良好的分离，阻碍了自组装和聚集，从而实现了去凝胶化和溶解改善。本研究强调了认识某些共无定形制剂凝胶化潜力的重要性，并为开发高质量的共无定形药物产品提供了一种有效的消除凝胶化的策略。
