微管蛋白抑制剂SUD-35固体分散体的制备、鉴定及初步体外药效学研究

Preparation, Physicochemical Characterization and Pharmacodynamics in Vitro of Solid Dispersion of Antitubulin SUD-35

关键词:  微管蛋白抑制剂  固体分散体  溶出速率  聚乙二醇6000  药效学

Key words:  antitubulin  solid dispersion  dissolution rate  PEG6000  pharmacodynamics

摘要:

目的 将难溶性微管蛋白抑制剂SUD-35制备成固体分散体，以增加其溶解度及溶出速率。方法 以聚乙二醇6000为载体，溶剂-熔融法制备SUD-35固体分散体。采用差示扫描量热分析与X-射线衍射观察药物在载体中的存在状态，并进行溶解度和体外溶出度研究。采用MTT法对SUD-35固体分散体对小鼠白血病L1210细胞药效进行测定。结果 SUD-35固体分散体中SUD-35的溶解度和溶出速率相对原料药和物理混合物均有明显提高，差示扫描量热分析与X-射线衍射结果显示SUD-35以无定型状态存在于固体分散体中，细胞药效结果显示SUD-35固体分散体对小鼠白血病L1210细胞增殖抑制率强于SUD-35纯药。结论 聚乙二醇 6000为载体制备SUD-35固体分散体，可显著提高SUD-35的溶解度及溶出速率。

Abstract:

OBJECTIVE To prepare antitubulin SUD-35 solid dispersion from poorly-soluble SUD-35 so as to improve its solubility and dissolution rate in vitro. METHODS Solid dispersions of SUD-35 were prepared by solvent-fusion method with PEG6000 as carrier. The status of SUD-35 in carrier was determined by differential scanning calorimetry(DSC) and X-ray diffractometry(XRD). The solubility and the dissolution rate of the solid dispersion in vitro were studied. The cytotoxicities of SUD-35 in solid dispersion to the L1210 cells were assayed by MTT method. RESULTS The results showed that the solubility and dissolution rate of SUD-35 was significantly improved by solid dispersion compared to that of the pure drug and physical mixture. The results of DSC and XRD showed that the SUD-35 insolid dispersion was amorphous form. Cytotoxicity study suggested that the inhibitory rates of SUD-35-PEG6000 solid dispersion to L1210 cells were higher than that of pure SUD-35. CONCLUSION The solubility and dissolution rates of SUD-35 were improved by solid dispersion technique.