卡维地洛-PVPVA64固体分散体的制备与表征

目地：制备卡维地洛的固体分散体，提高其在水中的溶解度和溶出度。方法：以乙烯基吡咯烷酮／醋酸乙烯共聚物（PVPVA64）为载体，无水乙醇为溶剂，制备卡维地洛固体分散体，并通过差示扫描量热法、x-射线粉末衍射法、红外分光光度法、原子力显微镜扫描、溶解度测定、溶出度实验及稳定性试验对固体分散体进行表征。结果：差示扫描量热法、x-射线粉末衍射法以及原子力显微镜扫描的谱图和图像分析表明卡维地洛以无定形状态存在于制得的固体分散体中，而傅里叶变换红外光谱分析则表明在固体分散体中卡维地洛与PVPVA64间可能以氢键结合形式存在。与卡维地洛原料药相比，该固体分散体的溶解度提高了80倍，且1h溶出百分率也从10％以下提高到95．5％。经差示扫描量热法、x-射线粉末衍射法及溶出度实验考察发现，在温度为40℃、相对湿度为75％的环境条件下，于90d内，该固体分散体稳定性良好。结论：卡维地洛与PVPVA64形成固体分散体后可显著提高其溶解度和溶出度，且热力学稳定，可进一步用于制备生物利用度更高的口服固体剂型。

Preparation and Characterization of Solid Dispersion of Carvedilol with PVPVA64

Objective:To prepare carvedilol solid dispersion to improve its solubility and dissolution in water.Methods:Carvedilol solid dispersion was prepared using poly(N-vinylpyrrolidone/vinyl acetate)(PVPVA64) as carrier and absolute alcohol as solvent.The solid dispersion was characterized by diffe-rential scanning calorimetry(DSC),powder X-ray diffractometry(PXRD),Fourier-transformed infrared spectrophotometry(FTIR) and atomic force microscopy(AFM) as well as solubility,dissolution and stability tests.Results:It was shown that carvedilol existed in amorphous state and probably in hydrogen bonding form in the prepared solid dispersion by DSC,PXRD,AFM and FTIR,individually.There was an 80-fold increase in solubility of carvedilol after the formation of solid dispersion and the 1 h-dissolution percentage was also increased from less than 10% to 95.5% compared with the pure drug powder.Furthermore,it was found that the solid dispersion had better stability at 40 ℃ under relative humidity of 75% for 90d by DSC,PXRD and dissolution test.Conclusion:The solubility and dissolution of carvedilol forming the solid dispersion with PVPVA64 could be increased significantly.The solid dispersion has a favorable thermo-stability,and shows the promising application in developing the oral solid dosage form of carvedilol with enhanced bioavailability.