The importance of solidification stress on the redispersibility of solid nanocrystals loaded with harmine.
The importance of solidification stress on the redispersibility of solid nanocrystals loaded with harmine.
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DOI：
10.1016/j.ijpharm.2015.01.037
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发表时间：
2015-03
影响因子：
5.8
通讯作者：
Pengfei Yue;Changhong Wang;Jixiu Dan;Wei Liu;Zhenfeng Wu;Ming Yang
中科院分区：
文献类型：
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作者：
Pengfei Yue;Changhong Wang;Jixiu Dan;Wei Liu;Zhenfeng Wu;Ming Yang
由于对固化应力对药物纳米晶再分散性影响的认识有限，本文系统地研究了稳定剂和冷冻保护剂的不同类型和浓度以及固化温度对纳米晶再分散性的影响。通过冷冻、冻干和喷雾干燥等不同应力的凝固过程，将毒碱纳米悬浮液转化为毒碱固体纳米晶体（HAR-SNC）。研究了不同浓度的稳定剂和冷冻保护剂对HAR-SNC再分散性的影响。结果表明：HAR-SNC在强冻结温度应力下的再分散性优于保守和中等冻结温度条件下的再分散性；HPMC能有效地保护HAR-SNC在冻干过程中不受破坏，使其均匀吸附在纳米晶体表面，防止团聚。蔗糖和山梨醇在冻干过程中对HAR-SNC的结晶生长具有良好的保护作用。在喷雾干燥过程中，由于高粘度聚合物稳定剂的位阻效应，CMS-Na在保护HAR-SNC免遭破坏方面发挥了突出的作用。结果表明，HAR-SNC在凝固过程中发生了团聚或晶体生长，其团聚或晶体生长的程度随稳定剂的种类、用量以及施加的应力条件的不同而不同。高分子稳定剂对HAR-SNC在凝固过程中的损伤保护效果较好。
Due to limited understanding about effect of solidification stress on the redispersibility of drug nanocrystals, the impact of the different type and concentration of stabilizers and cryoprotectants, as well as the solidification temperature on the redispersibility of nanocrystals were systematically investigated. Harmine nanosuspensions were transformed into harmine solid nanocrystals (HAR-SNC) via different stress of solidification process including freezing, lyophilization and spray-drying. The effect of different concentrations of stabilizers and cryoprotectants on redispersibility of HAR-SNC was also investigated, respectively. The results showed that the redispersibility of HAR-SNC at the aggressive freezing temperature stress was better more than those of conservative and moderate stress condition. The HPMC was effective enough to protect HAR-SNC from damage during lyophilization, which could homogeneously be adsorbed into the surface of nanocrystals to prevent the agglomerates. The sucrose and sorbitol achieved excellent performance that protected HAR-SNC from crystal growth during lyophilization. The CMS-Na played an outstanding role in protecting the HAR-SNC from breakage during spray-drying, due to the steric barrier effect of high viscosity polymeric stabilizers. It was concluded that HAR-SNC was subjected to agglomeration or crystal growth during solidification, and the degree of agglomeration or crystal growth varied with the type and the amounts of stabilizers used, as well as stress conditions applied. The polymeric stabilizers were more effective to protect HAR-SNC from the damage during solidification process.