依折麦布固体分散体的制备及其体外溶出

Preparation and evalution of ezetimibe solid dispersions in vitro

目的制备难溶性药物依折麦布固体分散体,改善其溶出性质,为固体分散体技术提高难溶性药物溶出及生物利用度提供新的参考。方法以共聚维酮(polyvinyl pyrrolidone-vinyl acetate copolymer,PVP VA64)作为亲水性载体材料,采用溶剂挥发法制备不同处方的依折麦布固体分散体,并进行溶出度考察;通过红外光谱法、差式扫描量热法及X射线衍射法对依折麦布固体分散体进行表征与评价。结果依折麦布与PVP VA64的质量比为1∶10时,依折麦布在质量分数0.1%十二烷基硫酸钠醋酸盐缓冲液中30 min累积溶出接近100%,与物理混合物相比,显著提高了依折麦布固体分散体的体外溶出度,物态鉴别表明依折麦布以无定型状态存在于载体中。结论制备依折麦布PVP VA64固体分散体,可显著提高其体外溶出度。

Objective To prepare ezetimibe solid dispersions to promote the dissolution of ezetimibe. Methods Ezetimibe binary solid dispersions were prepared by solvent evaporation method with poly vinylpyrrolidone-vinyl acetate copolymer（ PVP-VA; Kollidon VA64）at various weight ratios as the carrier. The solid dispersions were characterized and evaluated by Fourier transform infrared spectroscopy, different scanning calorimetry and power X-ray diffraction. Results The optimized solid dispersion formulation （ m： m = 1 ： 10） showed nearly complete dissolution within 30 min in the medium of 0. 1% SDS acetate buffer pH 4. 5, which was significantly higher than that of the pure drug and physical mixture. The results of Fourier transform infrared spectroscopy, different scanning calorimetry and power X-ray diffraction revealed that ezetimibe existed as amorphous form in the formulation. Conclusions Ezetimibe solid dispersions are successfully prepared by solvent evaporation method, which could increase the in vitro dissolution of ezetimibe.