基于固体分散技术的山楂叶总黄酮缓释胶囊的研制及释药机制研究

Study on the Preparation and Drug Release Mechanism of Hawthorn Leaf Total Flavonoids Sustained Release Capsules Based on Solid Dispersion Technology

目的研制山楂叶总黄酮缓释胶囊,并考察其释药机制。方法采用喷雾干燥法制备山楂叶总黄酮缓释固体分散体,以乙基纤维素等为载体,以2,6,12 h的释放度为指标,筛选最佳缓释固体分散体处方;采用X-射线衍射、扫描电镜和红外光谱法考察固体分散体中药物分散状态;拟合川北方程,以粉体流动性参数为指标,筛选缓释胶囊的处方辅料,制备山楂叶总黄酮缓释固体分散体胶囊,考察缓释胶囊释药机制,拟合释放动力学方程。结果山楂叶总黄酮缓释固体分散体最佳处方组成为山楂叶总黄酮∶乙基纤维素∶卡波姆940P=4∶1∶0.5;X-射线衍射和扫描电镜结果表明,药物以无定形或分子形式分散于固体分散体中;红外光谱法结果表明,乙基纤维素峰强度增强;缓释胶囊最佳处方组成为固体分散体∶微粉硅胶=1∶0.3%,所制备缓释胶囊释放度2,6,12 h分别为27.56%,69.50%和96.78%。结论该缓释胶囊在12 h内呈现良好缓释特征,释放行为符合一级动力学方程,释放机制为扩散和溶蚀相结合机制,且为降解控释型。

OBJECTIVE To prepare Hawthorn leaves flavonoids sustained release capsules and investigate the release mechanism. METHODS Hawthorn leaves flavonoids sustained release solid dispersion was prepared by spray drying method, using ethyl cellulose as carrier, with 2, 6 and 12 h of the cumulative release amount as index, to determine the best sustained release solid dispersion prescription. X-ray diffraction, scanningelectron microscopy and infrared spectroscopy were used to investigate the drug dispersionin state in the solid dispersion. Kawakita equation was fitted with the fluidity of the powder parameters as index to screen the prescriptions, prepare the Hawthorn leaves flavonoids sustained release capsules, investigate the release mechanism of the capsules and fit the release kinetics equation. RESULTS The best prescription of Hawthorn leaves flavonoids sustained release solid dispersion composition： Hawthorn leaves flavonoids∶ethyl cellulose∶carbopol =4∶1∶0.5; XRD and SEM results showed that the drug in amorphous form or molecular form dispersed in the sustained release solid dispersion. Infrared spectroscopy results showed that no interactions were between Hawthorn leaves flavonoids, ethyl cellulose and carbomer. The optimal sustained release capsules prescription was solid dispersion∶silica gel as 1∶0.3%. The sustained-release capsules by accumulative release percentage of 2 h was 27.56%, 6 h was 69.50%, 12 h was 96.78%. CONCLUSION The sustained-release capsules show good sustained release characteristics in 12 h. The release behavior conforms to the first-order kinetic equation, the release mechanism is the combination of diffusion and erosion, and the degradation of controlled release type.