无定形态药物结晶成核研究进展

Advances in crystal nucleation for amorphous drugs

无定形态固体分散体能显著提高难溶性药物的溶解度和生物利用度,但其在制备或储存过程中容易发生结晶而削弱原有的优势。固体分散体中的无定形态药物结晶过程分为成核和晶体生长两步,其中成核是结晶的起始环节和关键步骤,但目前尚对无定形态药物结晶成核认识还很有限。本文对无定形态药物成核的研究方法、成核理论、添加物影响成核的机制及成核影响因素进行归纳,期望为无定形态固体分散体处方设计和提高其物理稳定性提供理论指导。

Amorphous solid dispersion(ASD)is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs.However,maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD.Crystallization is a process of nucleation and crystal growth.The nucleation is the key factor that influences the physical stability of the ASD.However,a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available.We reviewed the methods and theories of nucleation for amorphous drug.Meanwhile,we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation.This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.