Key Lab of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine , Nanchang , China and.
Pharm Dev Technol. 2014 Sep;19(6):662-70. doi: 10.3109/10837450.2013.819015. Epub 2013 Jul 22.
To overcome the limitations of the conventional particle size reduction technologies, a novel combinative particle size reduction method for the effective production of homogeneous nanosuspensions was investigated. Ursodeoxycholic acid, a poorly soluble drug representative, was tried to prepare nanosuspension by homogenization technology and high-pressure precipitation tandem homogenization technology. It was shown that the combinative approach could significantly improve the particle size reduction effectiveness over conventional homogenization approach. The Box-Behnken design analysis for process optimization revealed that the acceptable UDCA-NS was obtained wherein the optimal values of A, B, C and D were 10%, 500 bar, 0.125 and 600 bar, respectively. SEM results demonstrated that no significant aggregation or crystals growth could be observed in the freeze-dried UDCA nanocrystals. The DSC and XRD results showed that UDCA remained in a crystalline state. Dissolution velocities of the freeze-dried UDCA-NS powder were distinctly superior compared to those of the crude powder and physical mixture. The high-pressure precipitation tandem homogenization technology can be a good choice for nanosuspension preparation of poorly soluble UDCA, due to high efficiency of particle size reduction.
为了克服传统粒径减小技术的局限性，研究了一种新颖的组合粒径减小方法，用于有效生产均一的纳米混悬剂。熊去氧胆酸是一种难溶性药物代表，尝试通过匀浆技术和高压沉淀串联匀浆技术制备纳米混悬剂。结果表明，组合方法可显著提高常规匀浆方法的粒径减小效果。工艺优化的 Box-Behnken 设计分析表明，可获得可接受的 UDCA-NS，其中 A、B、C 和 D 的最佳值分别为 10%、500bar、0.125 和 600bar。SEM 结果表明，冻干的 UDCA 纳米晶体中没有观察到明显的聚集或晶体生长。DSC 和 XRD 结果表明 UDCA 仍处于结晶状态。与原粉和物理混合物相比，冻干 UDCA-NS 粉末的溶解速度明显更快。由于粒径减小效率高，高压沉淀串联匀浆技术可作为制备难溶性 UDCA 纳米混悬剂的理想选择。
