“胆安合剂”缓释颗粒剂的研制及体内外评价  

Development and in vitro-in vivo pharmacokinetics evaluation of sustained-release granules of Dan′an mixture

作　　者：陈娜娜 牛婧娥 史彦斌[1] 丛朝彤 杨彦彪 张成安 朱宗杰 滕月鹏[3] 张志叶 Chen Na-na;Niu Jing-e;Shi Yan-bin;Cong Zhao-tong;Yang Yan-biao;Zhang Cheng-an;Zhu Zong-jie;Teng Yue-peng;Zhang Zhi-ye(School of Pharmacy,Lanzhou University,Lanzhou 730000,China;Department of Pharmacy,The First People's Hospital of Lanzhou,Lanzhou 730050,China;Department of Pharmacy,The Second People's Hospital of Lanzhou,Lanzhou 730046,China)

机构地区：[1]兰州大学药学院,甘肃兰州730000 [2]兰州市第一人民医院药剂科,甘肃兰州730050 [3]兰州市第二人民医院药剂科,甘肃兰州730046

出　　处：《兰州大学学报（医学版）》2020年第3期28-37,共10页Journal of Lanzhou University（Medical Sciences）

基　　金：Talent Innovation and Entrepreneurship Research project of Lanzhou(2014 RC-71);Gansu Natural Science Fund(17JR5RA216)。

摘　　要：目的通过胆康缓释颗粒的制备,以提高用于治疗慢性胆囊炎的中药医院制剂"胆安合剂"的生物利用度。方法通过浓缩"胆安合剂"得到浸膏,西黄蓍胶、壳聚糖和乙基纤维素作为阻滞剂,湿法制粒得到胆康缓释颗粒。以体外累积释放率为评价指标,响应面结合Box-Behnken设计优化胆康缓释颗粒处方。模拟消化道环境探讨指标性成分体外缓放机制,通过家兔药动学研究评价生物利用度。结果胆康缓释颗粒的最佳处方组成为:质量比为67.98%冷冻干燥的"胆安合剂"浸膏,5%西黄耆胶,14.48%壳聚糖和12.54%乙基纤维素。胆康缓释颗粒指标性成分黄芩苷在人工胃液中比在人工肠液中释放慢。黄芩苷在pH 1.2和7.0液体环境中的释放机制为一级释放,而在pH 6.8和7.4条件下为Fickian扩散。胆康缓释颗粒的生物半衰期约为"胆安合剂"的2倍,体内平均滞留时间显著延长,药时曲线下面积约为"胆安合剂"的3.5倍。结论胆康缓释颗粒可有效延长指标性成分黄芩苷的释放和消除,提高"胆安合剂"的生物利用度。胆康缓释颗粒有望在临床应用中成为"胆安合剂"的替代剂型。Objective Aimed at developing sustained-release granules of Dan′an mixture(SRG-DM), improving bioavailability of Dan′an mixture(DM) which is an effective hospital preparation of traditional Chinese medicine against chronic cholecystitis.Methods Extract was obtained by concentrating DM. SRG-DM was made with wet granulation method using tragacanth gum(TG), chitosan(CS) and ethylcellulose(EC) as retardants. Response surface methodology combined with Box-Behnken experimental design was applied to optimize the SRG-DM formulation with in vitro cumulative release percentage as the evaluation index. Results The in vitro and in vivo sustained-release properties of the optimized SRG-DM were separately investigated in simulated biological fluids and in rabbits. The optimal SRG-DM formulation consisted of a mass ratio of 67.98% freeze-dried DM extract, 5% TG, 14.48% CS and 12.54% EC. Baicalin, as a marker component and releasing from SRG-DM in acid solution, was slower than that in alkaline solution. The release mechanism was fitted to first-order kinetics in pH 1.2 and 7.0 dissolution medium, followed by the Fickian diffusion in pH 6.8 and 7.4. The biological half-time of SRG-DM was approximately two times longer than that of DM. The mean resident time of SRG-DM was significantly prolonged compared with that of DM. The area under the curve of SRG-DM was approximately 3.5-fold that of DM. Conclusion The newly developed SRG-DM can effectively sustain the release and elimination of marker component of baicalin, thus improving bioavailability of baicalin.SRG-DM is a promising alternative dose form to Dan′an mixture in practice.

关 键 词：胆康缓释颗粒 BOX-BEHNKEN设计 药物释放机制 药动学 

分 类 号：R944[医药卫生—药剂学]