Roy Harekrishna, Maddela Sudhir, Munagala Alekhya, Rahaman Shaik Abdul, Nandi Sisir
Department of Pharmaceutics, Nirmala College of Pharmacy, Mangalagiri, Guntur-522503, Andhra Pradesh, India.
Department of Pharmaceutical Chemistry, Global Institute of Pharmaceutical Education and Research, Affiliated to Uttarakhand Technical University, Kashipur-244713, India.
Comb Chem High Throughput Screen. 2021;24(10):1628-1643. doi: 10.2174/1386207323666201230094115.
The present investigation aimed to prepare metronidazole (MTZ) topical bigel for the effective delivery of MTZ and to study the effect of applied variables as per statistical design. The study also signifies the implementation of the statistical method using the Quality by Design technique for MTZ bigel.
The MTZ bigels were prepared as per the runs suggested by Box Behnken design (BBD) using statistical software. A total of 28 runs were suggested by the BBD, considering sodium carboxymethylcellulose (Na CMC), guar gum, hydrogel and RPM as independent variables. The prepared bigels were evaluated for organoleptic properties, percentage drug content, spreadability, viscosity, percentage in-vitro drug release, and antimicrobial efficacy. Model selectivity was ascertained by p-value considering responses along with predicted R and adjusted R values.The fitting of model was ascertained by F-value as well as "lack of fit" was carried out to find out the suitability of the experimental design. Furthermore, the characteristic distribution of data was ascertained by the "normal plot of residual" method. The compatibility of MTZ and excipients in bigels was confirmed by FTIR and the crystalline nature of MTZ in formulations was studied by DSC and XRD studies. Furthermore, the dispersion of bigel was assessed by the SEM study.
The effect of independent variables on spreadability (mm), viscosity (cp), pH, drug release in 6 hours (%)and drug content (%) was evaluated. The optimized formulation was selected and evaluated by a polynomial equation while considering the p-value. These variables showed a significant effect on responses. A less significant difference was observed (6.37, 14463, 6.97, 86.29, and 67.47, respectively, for spreadability, viscosity, pH, and percentage drug release and % drug content) between the observed and predicted values indicating the model's suitability. The prepared bigels were found to be compatible and globules uniformly dispersed throughout the bigel.
The 3D response surface design ascertained the optimal MTZ bigel at 1.25g of NaCMC, 0.5g of guargum, 37.5g hydrogel, and 1000 RPM. The selected bigel showed good antimicrobial efficacy against S. Aureus and may be considered an effective delivery vehicle for MTZ.
本研究旨在制备甲硝唑（MTZ）局部用双凝胶，以实现MTZ的有效递送，并根据统计设计研究应用变量的影响。该研究还表明了采用质量源于设计技术对MTZ双凝胶实施统计方法。
使用统计软件，按照Box Behnken设计（BBD）建议的实验方案制备MTZ双凝胶。BBD共建议了28个实验方案，将羧甲基纤维素钠（Na CMC）、瓜尔胶、水凝胶和转速作为自变量。对制备的双凝胶进行感官特性、药物含量百分比、铺展性、粘度、体外药物释放百分比和抗菌效果评估。通过考虑响应以及预测R值和调整后R值的p值来确定模型选择性。通过F值确定模型拟合度，并进行“失拟度”检验以确定实验设计的适用性。此外，通过“残差正态图”方法确定数据的特征分布。通过傅里叶变换红外光谱（FTIR）确认MTZ与双凝胶中辅料的相容性，并通过差示扫描量热法（DSC）和X射线衍射（XRD）研究制剂中MTZ的晶型性质。此外，通过扫描电子显微镜（SEM）研究评估双凝胶的分散情况。
评估了自变量对铺展性（mm）、粘度（cp）、pH值、6小时药物释放率（%）和药物含量（%）的影响。在考虑p值的情况下，通过多项式方程选择并评估了优化配方。这些变量对响应显示出显著影响。观察值与预测值之间的差异较小（铺展性、粘度、pH值、药物释放百分比和药物含量百分比分别为6.37、14463、6.97、86.29和67.47），表明模型适用。制备的双凝胶被发现具有相容性，球体均匀分散在整个双凝胶中。
三维响应面设计确定了在1.25g NaCMC、0.5g瓜尔胶、37.5g水凝胶和1000转/分钟条件下的最佳MTZ双凝胶。所选双凝胶对金黄色葡萄球菌显示出良好的抗菌效果，可被视为MTZ的有效递送载体。
