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.
Key words
docetaxel /
solid dispersion /
poloxamer 188 /
dissolution /
bioavailability
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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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