三清降糖方总苷缓释片的制备及其体内外相关性分析  

Preparation and in vitro-in vivo Correlation Analysis in Rabbits of Total Glycosides Sustained-Release Tablets of Sanqing Jiangtang Decoction

作　　者：吕立勋[1] 李唐棣[1] 赵琳琳[1] 赵利刚[1] 

机构地区：[1]河北联合大学药学院,河北唐山063000

出　　处：《中国实验方剂学杂志》2013年第22期23-26,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：唐山市科技计划项目(1113020112a)

摘　　要：目的:优选三清降糖方总苷缓释片的处方工艺并考察其体外释放情况及兔体内药动学。方法:以羟丙甲基纤维素为骨架材料,采用湿法制粒压片制备缓释片。以1,4,8,12 h的累积释放率为综合评价指标,通过正交试验考察羟丙甲基纤维素、微晶纤维素用量及淀粉-乳糖对三清降糖方总苷缓释片处方工艺的影响,测定自制缓释片的体外释放度和兔体内药动学参数。采用HPLC测定黄芩苷含量,色谱条件为Diamonsil C18色谱柱(4.6 mm×250 mm,5μm),流动相甲醇-0.4%磷酸(三乙胺调pH 3.0,48∶52),检测波长270 nm,流速1.0 mL·min-1,柱温室温,进样量20μL。结果:最佳处方为羟丙甲基纤维素20%,微晶纤维素1%,淀粉-乳糖(3∶1),5%聚乙烯吡咯烷酮乙醇为黏合剂;制备的三清降糖方总苷缓释片12 h累积释放率>90%。黄芩苷的体内过程以单室模型拟合较好,2种制剂的药动学参数t max,C max,AUC均存在显著性差异。结论:三清降糖方总苷缓释片的体外释放良好,在兔体内吸收具有良好的相关性,相对生物利用度显著提高,达到了缓释制剂的要求。Objective： To optimize prescription of total glycosides sustained-release tablets of Sanqing Jiangtang decoction, then investigate its in vitro release profile and pharmacokinetics in rabbits. Method： With hydroxypropyl methyl cellulose （HPMC） as matrix material, sustained-release tablets was prepared by wet granulation tableting technique. With cumulative release rates in 1, 4, 8, 12 h as comprehensive evaluation index, orthogonal test was adopted to investigate effects of HPMC amount, microcrystalline cellulose （MCC） consumption and starch-lactose on formulation technology, in vitro release and in vivo pharmacokinetics in rabbits of these prepared sustained-release tablets were determined. HPLC was used to determine the content of baicalin, mobile phase ofmethanol-0.4% phosphoric acid （pH adjusted to 3.0 by triethylamine, 48：52）, detection wavelength 270 nm. Result： Optimum prescription was the mass fraction of HPMC-K4M 20% , MCC 1% , starch and lactose as filler with dosage ratio of 3 ： 1, 5% PVP ethanol as binders; Cumulative release rate of these o prepared sustained-release tablets was 〉 90% in 12 h. In vivo release of baicalin fitted well with single compartment model, t C AUC of two preparations had significant differences. Conclusion： A good correction of in vitro release and in vivo absorption of total glycosides sustained release tablets prepared as optimized prescription was satisfied, the relative bioavailability significantly increased, which reached requirements of sustained-release formulations.

关 键 词：三清降糖方 缓释片 正交试验 体外释放度 体内外相关性 药代动力学研究 

分 类 号：R283.6[医药卫生—中药学]