本文基于“质量源于设计”(Quality by Design, QbD)理念设计并优化了氨来呫诺(Amlexanox, AML)亲水凝胶骨架缓释片(简称为“AML缓释片”)的处方工艺。在风险评估的基础上结合单因素考察结果和鱼骨分析法确定潜在关键工艺参数(Critical ...本文基于“质量源于设计”(Quality by Design, QbD)理念设计并优化了氨来呫诺(Amlexanox, AML)亲水凝胶骨架缓释片(简称为“AML缓释片”)的处方工艺。在风险评估的基础上结合单因素考察结果和鱼骨分析法确定潜在关键工艺参数(Critical process parameters, CPPs),采用Plackett-Burman设计对CPPs进行筛选,然后用Box-Behnken设计对CPPs进行优化,建立统计模型,对优化后的工艺进行验证并考察其体外释放行为。结果表明骨架材料用量、黏合剂用量和片剂硬度对片剂释放行为有显著影响,当三者分别为50%~55%、62.5%~100%(占干物料的量)、124~142N时制备的氨来呫诺亲水凝胶骨架缓释片能达到释放目标,即2、6、12、18、24 h的累积释放率分别为8%~10%、25%~30%、50%~55%、75%~80%、95%以上。基于QbD理念设计的氨来呫诺亲水凝胶骨架缓释片处方工艺稳定可行,符合制剂设计的释放要求,具有良好的商业前景。展开更多
A novel and sensitive stability indicating RP-HPLC method has been developed for the quantitative determination of amlexanox in bulk drugs. The separation was accomplished on C18 column using 10 mM ammonium dihydrogen...A novel and sensitive stability indicating RP-HPLC method has been developed for the quantitative determination of amlexanox in bulk drugs. The separation was accomplished on C18 column using 10 mM ammonium dihydrogen orthophosphate (pH adjusted to 4.8 by using ortho phosphoric acid) and methanol (30:70 v/v) as mobile phase in an isocratic elution mode at a flow rate of 1.0 mL min-1. The eluents were monitored by PDA detector at 245 nm. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Significant degradation was found under basic, acidic stress and UV light. The resolution (Rs) between amlexanox and its degradation products was found to be greater than 2.5. Regression analysis shows correlation coefficient greater than 0.999 for amlexanox. The inter and intraday precision values for amlexanox were found to be within 1.0% RSD. The method has shown good and consistent recoveries for amlexanox in bulk drugs (98.86% - 101.05%). The developed method was validated with respect to linearity, accuracy, precision and robustness.展开更多
文摘本文基于“质量源于设计”(Quality by Design, QbD)理念设计并优化了氨来呫诺(Amlexanox, AML)亲水凝胶骨架缓释片(简称为“AML缓释片”)的处方工艺。在风险评估的基础上结合单因素考察结果和鱼骨分析法确定潜在关键工艺参数(Critical process parameters, CPPs),采用Plackett-Burman设计对CPPs进行筛选,然后用Box-Behnken设计对CPPs进行优化,建立统计模型,对优化后的工艺进行验证并考察其体外释放行为。结果表明骨架材料用量、黏合剂用量和片剂硬度对片剂释放行为有显著影响,当三者分别为50%~55%、62.5%~100%(占干物料的量)、124~142N时制备的氨来呫诺亲水凝胶骨架缓释片能达到释放目标,即2、6、12、18、24 h的累积释放率分别为8%~10%、25%~30%、50%~55%、75%~80%、95%以上。基于QbD理念设计的氨来呫诺亲水凝胶骨架缓释片处方工艺稳定可行,符合制剂设计的释放要求,具有良好的商业前景。
文摘A novel and sensitive stability indicating RP-HPLC method has been developed for the quantitative determination of amlexanox in bulk drugs. The separation was accomplished on C18 column using 10 mM ammonium dihydrogen orthophosphate (pH adjusted to 4.8 by using ortho phosphoric acid) and methanol (30:70 v/v) as mobile phase in an isocratic elution mode at a flow rate of 1.0 mL min-1. The eluents were monitored by PDA detector at 245 nm. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Significant degradation was found under basic, acidic stress and UV light. The resolution (Rs) between amlexanox and its degradation products was found to be greater than 2.5. Regression analysis shows correlation coefficient greater than 0.999 for amlexanox. The inter and intraday precision values for amlexanox were found to be within 1.0% RSD. The method has shown good and consistent recoveries for amlexanox in bulk drugs (98.86% - 101.05%). The developed method was validated with respect to linearity, accuracy, precision and robustness.
