Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, 818 Xingwandadao Road, Nanchang, 330004, China.
Departments of Pharmacy, 94th Hospital of People's Liberation Army, Nanchang, China.
Arch Pharm Res. 2016 Oct;39(10):1404-1417. doi: 10.1007/s12272-016-0732-x. Epub 2016 Mar 23.
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.
由于对干燥过程中冷冻/热强度对药物纳米晶体再分散性的影响了解有限，本研究系统考察了不同类型和浓度的稳定剂和基质形成剂对纳米晶体再分散性的影响。将安非他命纳米混悬剂通过不同的干燥工艺转化为安非他命纳米晶体（Andro-NC）。结果表明，在剧烈冷冻强度（意味着更高的冷冻速率）下，Andro-NC 的再分散性优于在保守和中等条件下的再分散性。与干燥过程中的热应力相比，稳定剂的用量和类型更显著地影响了冻干过程中安非他命纳米晶体的再分散性。HPMC-蔗糖和 HPMC-山梨醇体系在冻干过程中表现出优异的性能，可保护 Andro-NC 免受晶体生长的影响。在喷雾干燥过程中，与热应力条件引起的影响相比，稳定剂的类型和用量对 Andro-NCP 再分散性的影响更为显著。Tg 较高的聚合物 HPMC、PVPK30 和 MCCS 在喷雾干燥过程中防止了 Andro-NCP 的破裂，这是由于聚合物稳定剂具有牢固的空间位阻效应。总之，Andro-NCP 在干燥过程中由于冷冻/热应力会发生团聚或晶体生长。聚合物稳定剂在固化过程中更有效地保护 Andro-NCP 免受冷冻/热损伤，在不同的固化应力下表现出强烈的表面吸附和高玻璃化转变特性。
