甘草苷胃漂浮片的制备、处方优化及对家兔胃黏膜保护作用研究

Preparation and formulation optimizing of liquiritin gastric floating tablets and protective effects on gastric mucosa injury of rabbits

目的:优化甘草苷胃漂浮片(liquiritin gastric floating tablets,Liq-GFT)处方,考察对家兔胃黏膜损伤的保护作用。方法:采用直接压片法制备Liq-GFT。选择HPMC K15M用量、硬脂酸用量和碳酸氢钠用量为自变量,Liq-GFT在2 h、6 h和12h累计释放度的综合评分为响应值,采用Box-Behnken响应面法优化处方,并研究Liq-GFT释药机制。将家兔分成正常组、模型组、Liq-GFT组和西咪替丁组,灌胃无水乙醇建立家兔胃黏膜损伤模型,评价Liq-GFT对胃黏膜损伤的保护作用。结果:Liq-GFT最佳处方为:HPMC K15M用量为26.4%,硬脂酸用量为6.6%,碳酸氢钠用量为9.0%。Liq-GFT平均漂浮时间达12 h,浮动滞后时间为58 s,12 h的累积释放度为91.3%。体外释药过程符合一级模型,释药机理为扩散与溶蚀协同。药效学结果显示Liq-GFT高剂量组(40 mg·kg^(-1)·d^(-1))胃黏膜损伤指数显著性下降(P<0.01),溃疡抑制率达48.92%。结论:LiqGFT体外缓释特征明显,累积释放度高,对家兔胃黏膜损伤保护作用明显。

OBJECTIVE To optimize formulations of liquiritin gastric floating tablets(Liq-GFT) and explore its protective effects on gastric mucosa injury of rabbits.METHODS Liq-GFT was prepared by powder compression.Amounts of HPMC K15M,stearic acid and NaHCO_(3) were employed as independent variables.And comprehensive score of cumulative release at 2/6/12 h was selected as evaluation parameters.The formulations of Liq-GFT were optimized by Box-Behnken response surface method and release mechanisms also elucidated.Rabbits were randomized into four groups of normal,model,Liq-GFT and cimetidine.Acute gastric mucosal injury model in rabbits was established by an intragastric injection of ethanol.And the protective effects of Liq-GFT on gastric mucosal injury were evaluated.RESULTS Optimal formulation of Liq-GFT:amounts of HPMC K15M,stearic acid and NaHCO_(3) were 26.4%,6.6% and 9.0%,respectively.Average floating time of Liq-GFT was up to 12 h,floating lag time 58 s,and cumulative release rate 91.3%.The release process of Liq-GFT in vitro accorded with the firstorder model and the release mechanism was through synergistic effects of diffusion and dissolution.Pharmacodynamic results indicated that gastric mucosal injury index of high-dose Liq-GFT group(40 mg·kg~(-1)·d~(-1)) decreased markedly as compared with model group(P<0.01) and ulcer inhibition rate was 48.92%.CONCLUSION Liq-GFT has obvious characteristics of sustained release in vitro.Its cumulative release rate is high and there are evident protective effects on gastric mucosa injury in rabbits.