摘要
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.
作者
王赟华
张家薇
杨峥
孙长柏
张付利
WANG Yunhua;ZHANG Jiawei;YANG Zheng;SUN Changbai;ZHANG Fuli(Department of Clinical Medicine,Zhengzhou Shuqing Medical College,Henan Zhengzhou 450064,China;School of Pharmacy,Henan University,Henan Kaifeng 475003,China)
出处
《中国医院药学杂志》
CAS
北大核心
2024年第21期2464-2469,共6页
Chinese Journal of Hospital Pharmacy
