目的：制备依折麦布／介孔硅固体分散体，以该固体分散体制备混悬剂，研究固体分散体和三甲基壳聚糖（TMC）对依折麦布药物动力学的影响。方法采用溶剂挥发法制备依折麦布／介孔硅固体分散体，以溶出度为指标筛选制备方法，采用差示扫描量热（DSC）、扫描电镜（SEM）等技术考察药物存在状态及物理稳定性。以甲基纤维素和 TMC分别为助悬剂，将依折麦布／介孔硅固体分散体制成混悬液，研究大鼠口服各混悬液的药物动力学。结果依折麦布与介孔硅质量比为1∶5，搅拌时间为6h，制得固体分散体的载药量为16．5％，药物以非晶状态存在，溶出度可达92．2％，AUC和 Cmax提高显著，tmax无明显变化。结论应用该固体分散技术和三甲基壳聚糖能改善依折麦布的口服吸收，提高生物利用度。%Objective To prepare ezetimibe/mesoporous solid dispersion ,and prepare suspension with solid dispersion ,and to investi‐gate the effect of solid dispersion and trimethylchitosan (TMC) on the pharmacokinetics .Methods The ezetimibe/mesoporous solid dispersion was prepared with solvent evaporation method that was screened using dissolution as index .The drug state in solid dis‐persion and physical stability were examined by DSC and SEM .The Ezetimibe Suspension was prepared by dispersing ezetimibe/mesoporous solid dispersion in solution of methylcellulose or TMC as suspending agents .The pharmacokinetics after orally admin‐istrating the suspensions was investigated in rat .Results The optimal weight ratio of drug to carrier was 1∶5 ;the stirring time was 6 h;the drug loading of solid dispersion was about 16 .5% ;the drug state in solid dispersion was not crystalline state ;the drug dis‐solution was up to 92 .2% ;AUC and Cmax were increased significantly ;but tmax had no significant change .Conclusion The applica‐tion of solid dispersion technique and TMC can improve the oral absorption of ezetimibe and increase the bioavailability of ezetimi‐be .
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