Formulation optimization of controlled release diclofenac sodium microspheres using factorial design
Formulation optimization of controlled release diclofenac sodium microspheres using factorial design
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DOI：
10.1016/s0168-3659(97)00102-8
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发表时间：
1998-02-12
影响因子：
10.8
通讯作者：
Amin, AF
中科院分区：
文献类型：
--
作者：
Gohel, MC;Amin, AF
双氯芬酸钠是一个理想的候选人纳入控释装置，以减少口服给药后的不良反应。以海藻酸钠为聚合物，氯化钙为交联剂制备微球。在本研究中，采用3(3)全因子设计来研究三个变量的联合影响。搅拌速度（X-1）、CaCl2浓度（X-2）和重质液体石蜡在分散介质（X-3）中的浓度（t(80)）和重质液体石蜡在药物溶出80%时的百分比。在实验设计中，海藻酸钠浓度、药物与海藻酸钠比等潜在变量保持恒定。导出了一个具有显著相互作用项的统计模型来预测t（80）。多元线性回归分析和f统计分析结果表明，制备微球时应采用较低的搅拌速度、较高的CaCl2浓度和较高的重质液体石蜡比例，以达到药物控释的目的。发现X1X2和X2X3相互作用在本质上具有统计学显著性。给出了X-1、X-2和X-3对t（80）的影响的响应面图。药物以异常型扩散释放。验证了该模型对药物释放谱的准确预测。在实验设计中确定了可接受批次，并对1、6和8 h内药物释放百分比进行了限制。(C) 1998 Elsevier Science B.V.
Diclofenac sodium is an ideal candidate for incorporation in a controlled release device to diminish its adverse effects after oral administration. Microspheres were prepared by using sodium alginate as a polymer and CaCl2 as a cross-linking agent. In this investigation, 3(3) full factorial design was used to investigate the joint influence of three variables. the stirring speed (X-1), concentration of CaCl2 (X-2) and % of heavy liquid paraffin in a blend of heavy and light liquid paraffin in the dispersion medium (X-3) on the time for 80% drug dissolution (t(80)). Potential variables such as concentration of sodium alginate and drug: sodium alginate ratio were kept constant in the experimental design. A statistical model with significant interaction terms is derived to predict t(80). The results of multiple linear regression analysis and F-statistics revealed that for obtaining controlled drug release, the microspheres should be prepared using relatively lower stirring speed, higher concentration of CaCl2 and higher percentage of heavy liquid paraffin in the dispersion medium. The X1X2 and X2X3 interactions were found to be statistically significant in nature. A response surface plot is presented to show the effects of X-1, X-2 and X-3 on t(80). The drug was released by diffusion of anomalous type. A model was validated for accurate prediction of drug release profile. Acceptable batches were identified in the experimental design with constraints on percentage drug released in 1, 6 and 8 h. (C) 1998 Elsevier Science B.V.