Chen Jie, Qiu Liyan, Hu Minxin, Jin Yi, Han Jieru
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Drug Dev Ind Pharm. 2008 Jun;34(6):588-94. doi: 10.1080/03639040701831835.
Solid dispersions using water-soluble carriers were studied for improving the dissolution of docetaxel, a poorly soluble compound. In order to obtain the most optimized formulation, we prepared many solid dispersions with different carriers, different solvents, or at a series of drug-to-carrier ratios, and compared their dissolution. The accumulative dissolution of docetaxel from poloxamer 188 was more excellent than that from PVP(k30) and glyceryl monostearate, and the dissolution of docetaxel from solid dispersion was markedly higher than that of pure docetaxel; meanwhile the increased dissolution was partly dependent on the ratios of docetaxel and poloxamer 188. The ethanol used to prepare solid dispersion is of more significant effect on the dissolution of docetaxel than that of acetone. The docetaxel/poloxamer 188 system was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and environmental scanning electron microscope (ESEM). The results of DSC, XRD, and ESEM analyses of docetaxel/poloxamer 188 system showed that there are intermolecular interactions between docetaxel and poloxamer, and the crystallinity of docetaxel disappeared. These results show that solid dispersion is a promising approach of developing docetaxel drug formulates.
为改善难溶性化合物多西他赛的溶出度，对使用水溶性载体的固体分散体进行了研究。为了获得最优化的制剂，我们制备了许多含有不同载体、不同溶剂或一系列药物与载体比例的固体分散体，并比较了它们的溶出度。多西他赛从泊洛沙姆188中的累积溶出度优于从PVP（K30）和单硬脂酸甘油酯中的溶出度，且多西他赛从固体分散体中的溶出度明显高于纯多西他赛；同时，溶出度的增加部分取决于多西他赛与泊洛沙姆188的比例。用于制备固体分散体的乙醇对多西他赛溶出度的影响比丙酮更大。采用差示扫描量热法（DSC）、X射线衍射法（XRD）和环境扫描电子显微镜（ESEM）对多西他赛/泊洛沙姆188体系进行了表征。多西他赛/泊洛沙姆188体系的DSC、XRD和ESEM分析结果表明，多西他赛与泊洛沙姆之间存在分子间相互作用，且多西他赛的结晶度消失。这些结果表明，固体分散体是开发多西他赛药物制剂的一种有前景的方法。
