摘要
目的优选多烯紫杉醇固体分散体的制备工艺,提高多烯紫杉醇的体外溶出度和绝对生物利用度。方法采用溶剂法制备不同载体,不同溶剂和不同药物载体比例的多烯紫杉醇固体分散体,并进行了体外溶出实验和大鼠体内生物利用度研究;同时采用XRD,DSC,ESEM法鉴别药物在固体分散体中的存在状态。结果泊洛沙姆188固体分散体对多烯紫杉醇增溶的效果优于PVPk30和单硬脂酸甘油酯;且溶出实验2h时,泊洛沙姆188固体分散体(10∶90)的累计溶出百分率接近于原料药的4倍;XRD,DSC、ESEM显示多烯紫杉醇在固体分散体中以无定型态或分子状态存在;高、低剂量大鼠口服给药的绝对生物利用度分别为10.1%和35.1%。结论固体分散体能明显提高多烯紫杉醇的体外溶出度和口服生物利用度。
Abstract
OBJECTIVE To optimize the preparation process of docetaxel solid dispersions and improve the dissolution and absolute bioavailability of docetaxel. METHODS Several kinds of docetaxel solid dispersions were prepared with different carriers, different solvent and different ratios of drug-to-carrier by solvent method, and then its dissolution in vitro and absolute bioavailability in rats was analyzed.The docetaxel status in solid dispersions was identified by XRD,DSC and ESEM. RESULTS It is found that the accumulative dissolution of docetaxel solid dispersion using poloxamer 188 as carrier was much better than that of using PVPk30 or glyceryl monostearate as the carriers of solid dispersions; and the accumulative dissolution of docetaxel solid dispersion using poloxamer 188 (10∶90) was about four times as much as that of pure drug substance at 2 h in dissolution test; the results of XRD,DSC and ESEM showed that docetaxel in solid dispersion was amorphous or molecular. After oral administration with high dose and low dose,the absolute bioavailabilities of docetaxel/poloxamer 188 solid dispersion were 10.1% and 35.1% separately in rats. CONCLUSION The dissolution in vitro and absolute bioavailability in rats after oral administration of docetaxel solid dispersion using poloxamer 188 as carrier was markedly improved.
关键词
多烯紫杉醇 /
固体分散体 /
泊洛沙姆188 /
溶出度 /
生物利用度
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Key words
docetaxel /
solid dispersion /
poloxamer 188 /
dissolution /
bioavailability
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陈洁;邱利焱;胡敏新;丛宁;金一.
多烯紫杉醇固体分散体的制备和体内外研究[J]. 中国药学杂志, 2007, 42(22): 1717-1722
CHEN Jie;QIU Li-yn;HU Min-xin;CONG Ning;JIN Yi.
Studies on Preparation and in Vitro and in Vivo Evaluation of Docetaxel Solid Dispersion [J]. Chinese Pharmaceutical Journal, 2007, 42(22): 1717-1722
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脚注
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