Roles of cryo/thermal strength for redispersibility of drug nanocrystals: a representative study with andrographolide
Roles of cryo/thermal strength for redispersibility of drug nanocrystals: a representative study with andrographolide
复制标题
DOI：
10.1007/s12272-016-0732-x
复制
发表时间：
2016-03
影响因子：
6.7
通讯作者：
Yuanbiao Xie;Yueqin Ma;Junnan Xu;Jixiu Dan;Pengfei Yue;Zhenfeng Wu;Mingming Yang;Qin Zheng
中科院分区：
文献类型：
--
作者：
Yuanbiao Xie;Yueqin Ma;Junnan Xu;Jixiu Dan;Pengfei Yue;Zhenfeng Wu;Mingming Yang;Qin Zheng
由于对干燥过程中的低温/热强度对药物纳米晶的复溶作用的了解有限，系统地研究了不同类型和浓度的稳定剂和基质形成剂对药物纳米晶复溶的影响。通过不同的干燥工艺将Andro纳米悬浮液转化为Andro纳米晶体（Andro-NC）。结果表明，Andro-NC在较强的冷冻强度（即较高的冷冻速率）下的冷冻效果优于在较弱和中等的冷冻强度下。与干燥产生的热应力相比，稳定剂的使用量和类型对冻干过程中Andro-NCP的稳定性影响更大。HPMC-蔗糖和HPMC-山梨糖醇系统实现了优异的性能，保护Andro-NC在冻干过程中免于晶体生长。在喷雾干燥过程中，稳定剂的种类和用量对Andro-NCP的回复性的影响比热胁迫条件下的影响更显著。由于高分子稳定剂具有牢固的空间位阻效应，具有高Tg的聚合物HPMC、PVPK 30和MCCS在防止Andro-NCP在喷雾干燥过程中断裂方面发挥了突出的作用。可以得出结论，Andro-NCP在干燥过程中由于低温/热应力而发生团聚或晶体生长。高分子稳定剂能更有效地保护Andro-NCP免受固化过程中的低温/热损伤，在不同的固化应力下表现出较强的表面吸附和较高的玻璃化转变性能。
Due to limited understanding about the effect of cryo/thermal strength from drying process on the redispersibility of drug nanocrystals, the impact of the different type and concentration of stabilizers and matrix formers on the redispersibility of nanocrystals were systematically investigated. Andro nanosuspensions were transformed into Andro nanocrystals (Andro-NC) via different drying process. The results demonstrated that the redispersibility of Andro-NC at the aggressive cryo-strength (meant higher freezing rate) was more excellent than those at conservative and moderate condition. Compared to the thermal stress from drying, the employed amount and type of stabilizers more dramatically affected the redispersibility of Andro-NCP during lyophilization. The HPMC-sucrose and HPMC-sorbitol system achieved excellent performance that protected Andro-NC from crystal growth during lyophilization. During spray-drying, the impacts of types and amounts of stabilizers on the redispersibility of Andro-NCP were more significant compared to those induced by the thermal stress conditions. The polymers HPMC, PVPK30 and MCCS with high Tg played an outstanding role in preventing the Andro-NCP from breakage during spray-drying, due to the firmly steric barrier effect of polymeric stabilizers. It is concluded that Andro-NCP is subjected to agglomeration or crystal growth due to cryo/thermal stresses during drying. The polymeric stabilizers are more effective to protect Andro-NCP from the cryo/thermal damage during solidification process, which behaved strong surface adsorption and high glass transition property at different solidification stress.