喜树碱微粉的制备工艺、溶出及生物利用度特征研究

目的对难溶性药物喜树碱(camptothecin)进行微粉化研究。方法借助乳化机和高压均质机采用乳化法制备喜树碱微粉,单因素法优化制备工艺。将最优乳化条件下得到的喜树碱微粉(camptothecin micronized powder)进行溶出和生物利用度研究。结果最佳制备工艺条件为聚山梨酯-80用量为0.4%,喜树碱在三氯甲烷-甲醇(8∶2)混合溶剂中的质量浓度为1 mg/m L,水相和油相体积比为7∶3,匀浆速率为7 000 r/min;匀浆时间为11 min。最佳工艺条件下得到的喜树碱微粉水中复溶后的粒径为(165.6±5.3)nm。扫描电镜结果显示喜树碱微粉呈现规则的长条状,颗粒大小比较均匀。溶出研究结果表明喜树碱微粉溶解度和溶出速率比原粉分别提高了1.36倍和4.09倍。口服生物利用度结果表明,与原料药相比,微粉化的喜树碱在大鼠体内的相对生物利用度提高了2.10倍。GC检测结果表明,喜树碱微粉溶剂残留符合ICH标准。结论乳化法制备喜树碱微粉后,改善了喜树碱原粉的溶解度和溶出速率,口服生物利用度得到提高。

Preparation, dissolution, and bioavailability characteristics of camptothecin micronized powder

Objective Camptothecin (CPT) as a kind of poorly soluble drug was conducted micronization research. Methods CPT micronized powder was prepared by emulsification method using emulsification machine and high pressure homogenizer. Moreover, single factor method was utilized to optimize. Dissolution and oral bioavailability study on CPT micronized powder prepared under the best emulsification conditions was conducted. Results The best preparation conditions were as follows:The dosage of Tween-80 as the surfactant was 0.4%; The concentration of CPT in chloroform-methanol (8:2) mixed solution was 1 mg/mL; The volume ratio of water-organic phase was 7:3; The homogenate speed was 7 000 r/min for 11 min. The particle size of CPT micronized powder prepared under the optimized conditions was (165.6±5.3) nm. The scanning electron microscopy (SEM) results showed that CPT micronized powder presented regular strip shape and uniform particle size. The dissolution study indicated that the solubility and dissolution rate of CPT micronized powder was increased by 1.36 and 4.09 times compared with the raw CPT powder. The results of oral bioavailability showed that compared with the raw CPT powder, the relative bioavailability of CPT micronized powder in mice was increased by 2.10 times. The results of gas chromatography showed that residual solvents in CPT micronized powder accorded with the standard of ICH. Conclusion Solubility and dissolution rate of CPT are both improved since CPT micronized powder is prepared by emulsification method. So the oral bioavailability is also improved.