药物无定形的转晶及其抑制策略

Crystallization of Amorphous Drugs and Inhibiting Strategies

与药物晶态相比,无定形态具有更高的表面自由能、更高的表观溶解度和更快的溶出速率。然而,药物无定形态属于热力学不稳定体系,易向稳定的晶态转变而减缓药物的溶出度,进而降低其生物利用度。本文主要介绍了药物无定形态的本质、结晶理论、物理稳定性的影响因素以及抑制转晶的策略,为合理设计无定形药物产品和有效开发无定形制剂提供理论指导,有助于无定形技术在解决药物难溶性问题中发挥更广泛的应用。

In comparison to the crystalline forms,amorphous drugs exhibit higher surface free energy,higher apparent solubility and faster dissolution rate.However,since the amorphous state is thermodynamically unstable,amorphous solids tend to transform into their stable crystalline forms,resulting in the decreased dissolution and hence low bioavailability.This paper reviews the fundamental introduction of amorphous drugs,the crystallization theory,the influence factors on the physical stability and strategies for their crystallization inhibition,in order to provide a theoretical guidance for the rational design of amorphous drug products and efficient development of amorphous formulations.All of these could contribute to more applications of amorphous drugs in overcoming the poor water solubility issues.