Mechanistic insight into gel formation of co-amorphous resveratrol and piperine during dissolution process

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 Tg 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.