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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1 h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90 d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。
Purpose: To prepare a solid dispersion of carvedilol to increase its solubility and dissolution in water. Methods: The solid dispersion of carvedilol was prepared by using vinylpyrrolidone / vinyl acetate copolymer (PVPVA64) as carrier and anhydrous ethanol as solvent. The dispersions were characterized by differential scanning calorimetry, X-ray powder diffraction, Spectrophotometry, atomic force microscopy, solubility measurement, dissolution test and stability test were used to characterize the solid dispersions. Results: Spectra and image analysis of differential scanning calorimetry, X-ray powder diffraction, and atomic force microscopy scans showed that carvedilol was present in the resulting solid dispersion in an amorphous state, while Fourier transform infrared Spectral analysis showed that there may be hydrogen bonding between carvedilol and PVPVA64 in the solid dispersion. Compared with the carvedilol API, the solubility of the solid dispersion increased by 80 times, and the percentage of dissolution at 1 h was also increased from below 10% to 95.5%. The results of differential scanning calorimetry, X-ray powder diffraction and dissolution show that the solid dispersion has a good stability within 90 d at a temperature of 40 ℃ and a relative humidity of 75%. Conclusion: The formation of solid dispersion of carvedilol and PVPVA64 can significantly improve its solubility and dissolution, and thermodynamically stable, and can be further used for the preparation of oral solid dosage forms with higher bioavailability.