长春西汀凝胶骨架片中枸橼酸和介质pH值对药物释放的影响

Influence of citric acid and pH value of dissolution medium on vinpocetine release from hydrophilic matrix tablets

目的 研究长春西汀凝胶缓释片中枸橼酸和介质pH值对药物释放行为和释放机制的影响。方法 测定长春西汀在不同pH值介质中的溶解度 ;以HPMC为骨架材料制备长春西汀骨架片 ,考察枸橼酸用量以及释放介质对药物释放行为的影响 ;每组体外释放曲线均采用Peppas公式 :Mt Minf=ktn 进行拟合 ,根据n值判断枸橼酸对药物释放机制的影响。结果 长春西汀溶解度随pH值升高而显著降低 ;枸橼酸的用量和不同释放介质对药物的释放行为均有显著影响 ;随着枸橼酸用量的增加 ,拟合参数n值都呈线性下降 ,k值都呈线性升高。结论 药物从HPMC凝胶骨架片中的释放速度显著依赖于片剂中枸橼酸的用量和介质pH值 ,调节枸橼酸的用量可以控制药物的体外释放时间 ;随着枸橼酸用量的不断增加 ,药物释放机制更靠近扩散过程 ,且释药速度逐渐增加。

OBJECTIVE: To investigate the influence of admixed citric acid and pH value of dissolution medium on the release behavior and release mechanism of vinpocetine from HPMC matrix tablets. METHODS: The solubility of vinpocetine in different mediums with different pH values was determined; Influence of citric acid and dissolution medium on the release behavior and release mechanism of vinpocetine from HPMC matrix tablets was investigated. Drug release profiles were described by Peppas equation: Mt/Minf = kt n, and the influence of citric acid on the dissolution mechanism was estimated according to the regression parameter-n values. RESULTS: With pH values of mediums increasing, the solubility of vinpocetine decreased significantly. The amounts of citric acid and the dissolution medium significantly influenced the drug release behavior and mechanism. Moreover, increasing content of citric acid produced decreasing values of n and increasing values of k, in a linear relationship. CONCLUSION: The release rate of vinpocetine from HPMC hydrophilic matrix tablets significantly depended on the amount of citric acid admixed in formulation and pH value of dissolution, and the drug release could be controlled by changing the content of citric acid added to the HPMC matrices. When increasing the quantities of citric acid, there was a trend favoring the mechanism of diffusion and the dissolution rates increased.