山楂叶总黄酮缓释胶囊的研制及释药机制考察

Preparation and release mechanism of hawthorn leaves flavonoids sustained release capsules

目的:研制山楂叶总黄酮缓释胶囊,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和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=4∶1∶0.5;X-射线衍射法(XRD)和扫描电镜法(SEM)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(山楂叶总黄酮∶乙基纤维素∶卡波姆=4∶1∶0.5)∶微粉硅胶为1∶0.3%,所制备缓释胶囊释放度2 h为27.56%,6 h为69.50%,12 h为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 the cumulative release amount at 2,6 and 12 h as index to determine the best prescription. The drug dispersionin state in the solid dispersion was investigated by using X-ray diffraction,scanning electron microscopy and infrared spectroscopy; the Kawakita equation was fitted; the prescriptions were screened with the fluidity of the powder parameters as index to prepare hawthorn leaves flavonoids sustained release capsules. The release mechanism of the capsules was investigate and the release kinetic equation was fitted.Results： The best prescription of hawthorn leaves flavonoids sustained release solid dispersion was as follows：hawthorn leaves flavonoids∶ ethyl cellulose∶ carbopol = 4∶ 1∶ 0. 5. XRD and SEM showed that the drug was dispersed in amorphous form or molecular form in the sustained release solid dispersion; infrared spectroscopy results showed that no interactions existed between hawthorn leaves flavonoids,ethyl cellulose,and carbomer; the optimal prescription for the sustained release capsules was as below： solid dispersion ∶ silica gel = 1 ∶ 0. 3%; the accumulative release percentage of the sustained-release capsules at 2,6,and 12 h was 27. 56%,69. 50%,and 96. 78%,respectively.Conclusion： The sustained-release capsules posses good sustained release characteristics within 12 h. The releasebehavior conforms to the first-order kinetic equation. The release mechanism is the combination of diffusion and erosion,and belongs to the degrdation-controlled release type.