Division of Pharmaceutics, Freeze Drying Focus Group, University of Erlangen, 91058 Erlangen, Germany.
J Pharm Sci. 2011 May;100(5):1958-68. doi: 10.1002/jps.22425. Epub 2010 Dec 10.
It has been recently reported in the literature that using a fast freezing rate during freeze-drying of drug nanosuspensions is beneficial to preserve the original particle size distribution. All freezing rates studied were obtained by utilizing a custom-made apparatus and were then indirectly related to conventional vial freeze-drying. However, a standard freeze-dryer is only capable of achieving moderate freezing rates in the shelf fluid circulation system. Therefore, it was the purpose of the present study to evaluate the possibility to establish a typical freezing protocol applicable to a standard freeze-drying unit in combination with an adequate choice of cryoprotective excipients and steric stabilizers to preserve the original particle size distribution. Six different drug nanosuspensions containing itraconazole as a drug model were studied using freeze-thaw experiments and a full factorial design to reveal major factors for the stabilization of drug nanosuspensions and the corresponding interactions. In contrast to previous reports, the freezing regime showed no significant influence on preserving the original particle size distribution, suggesting that the concentrations of both the steric stabilizer and the cryoprotective agent are optimized. Moreover, it could be pinpointed that the combined effect of steric stabilizer and cryoprotectant clearly contribute to nanoparticle stability.
最近有文献报道，在药物纳米混悬剂冷冻干燥过程中使用快速冷冻速率有利于保持原始粒径分布。所有研究的冷冻速率都是通过使用定制的设备获得的，然后与常规小瓶冷冻干燥间接相关。然而，标准冷冻干燥器仅能够在搁板流体循环系统中实现中等的冷冻速率。因此，本研究的目的是评估在结合适当选择的冷冻保护赋形剂和空间位阻稳定剂的情况下，为标准冷冻干燥装置建立典型冷冻方案的可能性，以保持原始粒径分布。使用冻融实验和全因子设计研究了六种含有伊曲康唑作为药物模型的不同药物纳米混悬剂，以揭示稳定药物纳米混悬剂的主要因素及其相应的相互作用。与之前的报道相反，冷冻条件对保持原始粒径分布没有显著影响，这表明空间位阻稳定剂和冷冻保护剂的浓度都得到了优化。此外，可以指出，空间位阻稳定剂和冷冻保护剂的联合作用显然有助于纳米颗粒的稳定性。
