Lu Enxian, Li Shoufeng, Wang Zhongqin
Shanghai Aucta Pharmaceuticals Co., Ltd., No. 3377 Kangxin Road. SIMZ Pudong, Shanghai 201318, China.
Asian J Pharm Sci. 2017 Jan;12(1):9-20. doi: 10.1016/j.ajps.2016.10.002. Epub 2016 Dec 8.
Supersaturable formulation can generate supersaturation after dissolution, providing kinetic advantage . However, the supersaturation may precipitate before being absorbed, which makes it difficult to ensure and predict its performance. The traditional USP method is typically for Quality Control (QC) purpose and cannot be used to predict the formulation in performance. Therefore, there is generally a lack of a predictive biorelevant testing method. In this review, different types of supersaturable formulations are described, including amorphous dispersions, polymorphs, salts/co-crystals, weak base and supersaturable solubilized formulations. Different kinds of dissolution methods for supersaturable formulations are also reviewed and discussed. Most of the methods take the physiology of gastrointestinal (GI) track into consideration, allowing reasonable prediction of the performance of supersaturable formulation. However, absorbing drug from GI track into blood stream is a complicate process, which can be affected by different processes such as transporter and metabolism. These factors cannot be captured by the testing. Thus, combining biorelevant dissolution methods with physiology-based pharmacokinetic modeling is a better way for the product development of supersaturable formulation.
过饱和制剂在溶解后可产生过饱和度，具有动力学优势。然而，过饱和度可能在吸收前就沉淀下来，这使得难以确保和预测其性能。传统的美国药典方法通常用于质量控制（QC）目的，不能用于预测制剂的性能。因此，普遍缺乏一种具有预测性的生物相关性测试方法。在本综述中，描述了不同类型的过饱和制剂，包括无定形分散体、多晶型物、盐/共晶体、弱碱和过饱和增溶制剂。还对过饱和制剂的不同溶解方法进行了综述和讨论。大多数方法都考虑了胃肠道（GI）的生理情况，从而能够合理预测过饱和制剂的性能。然而，药物从胃肠道吸收进入血流是一个复杂的过程，会受到转运体和代谢等不同过程的影响。这些因素无法通过测试来捕捉。因此，将生物相关性溶解方法与基于生理学的药代动力学建模相结合是过饱和制剂产品开发的更好方法。
