热熔挤出技术制备依帕司他固体分散体

Preparation of Epalrestat Solid Dispersion by Hot-Melt Extrusion Technique

目的采用热熔挤出(holt-melt extrusion,HME)技术制备高熔点难溶性药物依帕司他(epalrestat,EP)的固体分散体(solid dispersion,SD),提高其体外溶出度。方法以依帕司他的体外溶出度为指标,运用热熔挤出技术在低于药物熔点的温度下制备依帕司他固体分散体,考察不同载体和比例对溶出度的影响,筛选出最优处方。并采用X射线粉末衍射(XRD)、傅里叶变换红外光谱(FT-IR)和差示扫描量热法(DSC)对其物相进行研究。结果以Poloxamer 188为载体,药物与Poloxamer 188的比例为1∶3时,采用热熔挤出技术制备的固体分散体能够显著提高依帕司他的体外溶出度。XRD、FT-IR、DSC分析显示,依帕司他在固体分散体中以无定型态存在。结论载体可影响固体分散体中药物的溶出行为和物理状态。

OBJECTIVE To prepare epalrestat （EP） solid dispersion by holt-meh extrusion （HME） technique in order to enhance its dissolution rate. METHODS Optimal formula was obtained by screening the carrier type and drug proportion. The dispersion state of EP in the solid dispersion and physical mixture were studied with differential X-ray diffraction （X-RD） , Fourier transform infrared spectroscopy （FT-IR） and differential scanning calorimetry （DSC） analysis techniques. RESULTS Poloxamer 188 was selected as the carrier with the optimal ratio of Poloxamer188 to EP of 1： 3. The final solid powder product was homogeneous dispersion in light yellow color without any agglomerate. CONCLUSION The carrier of EP solid dispersion has significant impact on the dissolution behavior and state of EP. Using Poloxamer 188 as the carrier, holt-inch extrusion is an effective technology for improving the in vitro dissolution of EP.