Chappidi Suryaprakash Reddy, Bhargav Eranti, Marikunte Venkataranganna, Chinthaginjala Haranath, Vijaya Jyothi Mallela, Pisay Muralidhar, Jutur Mounika, Shaik Mahammad Mujahid, Poura Mrunalini, Yadav Sailaja, Syed Moinuddin
RERDS-CPR, Raghavendra Institute of Pharmaceutical Education and Research, Anantapur- 515721.
Connexios Life Sciences Pvt Ltd, Basavanagudi, Bangalore, 560004.
Adv Pharm Bull. 2019 Jun;9(2):281-288. doi: 10.15171/apb.2019.032. Epub 2019 Jun 1.
The purpose of the study was to develop and optimize rosiglitazone maleate mucoadhesive extended-release tablets by quality by design (QbD) approach. Based on QTPP (quality target product profile) CQAs (critical quality attributes) were identified. Failure mode and effects analysis (FMEA) method were adopted for risk assessment. Risk analysis by the evaluation of formulation and process parameters showed that the optimizing the levels of polymers could reduce high risk to achieve target profile. Drug-excipient compatibility studies by Fourier transforms infra-red and DSC studies showed that the drug was compatible with the polymers used. Design of experiment (DoE) performed by Sigma tech software, Carbopol 934P and sodium carboxymethyl cellulose (SCMC) were identified as independent variables and hardness, drug release at 12 hours and ex vivo mucoadhesion time were adopted as responses. Contour plots generated from the software were used for identification of design space. Carbopol 934P and SCMC had positive and negative effects respectively on the selected responses. Higher the concentration of Carbopol 934P and lower the concentration of SCMC mucoadhesive extended release criteria could be achieved. Drug release kinetics followed first order release with Higuchi diffusion and Fickian diffusion. Ex vivo mucoadhesion test on goat stomach mucosa indicated that adhesion time increased at higher concentrations of Carbopol 934P. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values, confirmed by calculating standard error. It has been concluded that the application of QbD in the optimization reduced the number of trials to produce a cost-effective formula.
本研究的目的是通过质量源于设计（QbD）方法来研发和优化马来酸罗格列酮黏膜黏附缓释片。基于质量目标产品概况（QTPP）确定了关键质量属性（CQA）。采用失效模式与效应分析（FMEA）方法进行风险评估。通过对处方和工艺参数的评估进行风险分析，结果表明优化聚合物用量可降低实现目标概况的高风险。通过傅里叶变换红外光谱和差示扫描量热法进行的药物 - 辅料相容性研究表明，药物与所用聚合物相容。使用Sigma tech软件进行实验设计（DoE），将卡波姆934P和羧甲基纤维素钠（SCMC）确定为自变量，将硬度、12小时药物释放量和体外黏膜黏附时间作为响应值。利用该软件生成的等高线图来确定设计空间。卡波姆934P和SCMC对所选响应值分别有正向和负向影响。卡波姆934P浓度越高且SCMC浓度越低，越能满足黏膜黏附缓释标准。药物释放动力学遵循一级释放，符合Higuchi扩散和Fickian扩散。对山羊胃黏膜进行的体外黏膜黏附试验表明，卡波姆934P浓度较高时黏附时间增加。选择并评估了满足所有所需参数的优化配方。通过计算标准误差证实，预测响应值与实验响应值密切吻合。得出的结论是，QbD在优化过程中的应用减少了试验次数，从而制得具有成本效益的配方。
