Polymorph transformation of solid drugs and inhibiting strategies

Abstract

Metastable forms and amorphous forms exhibit higher solubility and dissolution rates compared to stable crystalline forms, making them viable options for pharmaceuticals with low solubility. However, the use of metastable forms and amorphous forms may result in polymorph transformation in pharmaceutical manufacture and storage, which will reduce their bioavailability. Firstly, different polymorphic transformations were discussed. Then, the factors affecting crystals and amorphous stability, including solvent, temperature, humidity, and preparation processes were analyzed. Finally, strategies and their mechanisms to inhibit polymorphic transformation and amorphous recrystallization were also summarized, including suitable storage conditions, optimization of the preparation processes, use of additives, adjustment of formulation recipes, and surface and loading techniques.