Pu Xiaohui, Sun Jin, Wang Yan, Wang Yongjun, Liu Xiaohong, Zhang Peng, Tang Xing, Pan Weisan, Han Jihong, He Zhonggui
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Int J Pharm. 2009 Sep 8;379(1):167-73. doi: 10.1016/j.ijpharm.2009.05.062. Epub 2009 Jun 6.
The purpose of this study was to prepare and characterize nanosuspensions loading the active lactone form of 10-hydroxycamptothecin (10-HCPT). Nanosuspensions were prepared in terms of microprecipitation-high-pressure homogenization method. As for the preparation processes, three important parameters, i.e. the agitation rate of stabilizer solution, homogenization pressure and cycle numbers, were investigated and optimized, and the optimal values were 1000 rpm, 1000 bar and 20 times, respectively. The particle size and zeta potential of the 10-HCPT-nanosuspensions were 131 nm and -25.5 mV. The particle morphology was determined by transmission electron microscopy and the 10-HCPT nanoparticles were baculine or trabecular in shape. The solid state of 10-HCPT in nanoparticles was analyzed using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). The XRD and the DSC results both indicated that 10-HCPT was present as an amorphous state in the lyophilized powders for nanosuspension. The chemical stability tests demonstrated that near 90% lactone form of 10-HCPT was present in the nanosuspensions but it was easily transferred to the carboxylate form in the solution at pH 7.0-8.0. In vitro dissolution tests showed the dissolution rate of nanosuspensions, compared with the coarse suspensions, had been significantly increased.
本研究的目的是制备并表征负载10-羟基喜树碱（10-HCPT）活性内酯形式的纳米混悬液。采用微沉淀-高压均质法制备纳米混悬液。在制备过程中，研究并优化了三个重要参数，即稳定剂溶液的搅拌速率、均质压力和循环次数，其最佳值分别为1000 rpm、1000 bar和20次。10-HCPT纳米混悬液的粒径和zeta电位分别为131 nm和-25.5 mV。通过透射电子显微镜确定颗粒形态，10-HCPT纳米颗粒呈杆状或小梁状。使用X射线粉末衍射（XRD）和差示扫描量热法（DSC）分析纳米颗粒中10-HCPT的固态。XRD和DSC结果均表明，在纳米混悬液的冻干粉末中，10-HCPT以无定形状态存在。化学稳定性测试表明，纳米混悬液中存在近90%的10-HCPT内酯形式，但在pH 7.0-8.0的溶液中，它很容易转化为羧酸盐形式。体外溶出试验表明，与粗混悬液相比，纳米混悬液的溶出速率显著提高。
