Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, United States of America.
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, United States of America.
J Pharm Sci. 2023 Jan;112(1):19-35. doi: 10.1016/j.xphs.2022.08.029. Epub 2022 Aug 27.
The review summarizes the current state of knowledge of mannitol as an excipient in lyophilized injectable small and large molecule formulations. When compared with glycine, the physicochemical properties of mannitol make it a desirable and preferred bulking agent. Though mannitol is a popular bulking agent in freeze-dried formulations, its use may pose certain challenges such as vial breakage or its existence as a metastable crystalline hemihydrate in the final cake, necessitating appropriate mitigation strategies. The understanding of the phase behavior of mannitol in aqueous systems, during the various stages of freeze-drying, can be critical for the optimization of freeze-drying cycle parameters in multi-component formulations. Finally, using a decision tree as a guiding tool, we demonstrate the use of orthogonal techniques for attaining a stable and cost-effective lyophilized drug product containing mannitol.
本文综述了甘露醇作为冻干小分子量和大分子量制剂赋形剂的现有知识状态。与甘氨酸相比，甘露醇的物理化学性质使其成为一种理想且首选的增稠剂。尽管甘露醇是冻干制剂中常用的增稠剂，但它的使用可能会带来一些挑战，例如小瓶破裂，或者在最终的饼状物中以亚稳态结晶半水合物的形式存在，因此需要采取适当的缓解策略。了解甘露醇在水相体系中的相行为，在冻干的各个阶段，对于优化多组分制剂的冻干循环参数至关重要。最后，我们使用决策树作为指导工具，展示了如何使用正交技术获得含有甘露醇的稳定且具有成本效益的冻干药物产品。
