Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Road, Shanghai 201203, China; Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Road, Shanghai 201203, China.
Int J Pharm. 2015 Mar 1;480(1-2):107-15. doi: 10.1016/j.ijpharm.2015.01.037. Epub 2015 Jan 21.
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.
由于对固化工况下的固化应力对药物纳米晶再分散性的影响了解有限，因此系统研究了不同类型和浓度的稳定剂和抗冻剂以及固化温度对纳米晶再分散性的影响。将哈尔明纳米混悬液通过不同的固化工艺（包括冷冻、冻干和喷雾干燥）转化为哈尔明固态纳米晶（HAR-SNC）。还分别研究了不同浓度的稳定剂和抗冻剂对 HAR-SNC 再分散性的影响。结果表明，在剧烈冷冻温度应力下，HAR-SNC 的再分散性优于保守和中等应力条件下的再分散性。HPMC 在冻干过程中能够有效地保护 HAR-SNC 免受损伤，可以均匀地吸附到纳米晶表面，防止团聚。蔗糖和山梨醇在冻干过程中能出色地保护 HAR-SNC 防止晶体生长。CMS-Na 在喷雾干燥过程中对保护 HAR-SNC 免受破裂起到了卓越的作用，这是由于高粘度聚合物稳定剂的空间位阻效应。综上所述，HAR-SNC 在固化过程中会发生团聚或晶体生长，团聚或晶体生长的程度取决于所使用的稳定剂的类型和用量以及所施加的应力条件。聚合物稳定剂更有效地保护 HAR-SNC 免受固化过程中的损伤。
