Application of Box-Behnken Design for Validation of High-Performance Thin-Layer Chromatography/Densitometry Method for Robustness Determination of Apremilast in Bulk and in house Tablets

Pharmaceutical Methods Pub Date : 2017-10-15 DOI:10.5530/PHM.2018.1.3

Suraj R. Chaudhari, A. Shirkhedkar

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引用次数: 6

Abstract

Background: Apremilast is small molecule inhibitor of phosphodiesterase-4 (PDE-4) and an immunomodulating agent which is used for management of refractory psoriatic arthritis. Material and Methods: HighPerformance Thin-Layer Chromatography (HPTLC) method for the analysis of apremilast was developed and validated as per ICH guidelines. Apremilast was chromatographed on silica gel 60 F254 TLC plates using toluene: methanol (8:2 v/v) as a mobile phase. A Compact spot for apremilast was observed with Rf 0.64 ± 0.05, when the densitometric scanning was implemented at 230 nm. The linear regression analysis data for the calibration plots showed r2 > 0.99 with a concentration range from 250 – 1500 ng/band. ‘Design of Experiments’ (DoE) employing ‘Box-Behnken Design’ (BBD) and ‘Response Surface Methodology’ (RSM) were studied as an advancement to traditional ‘One Variable at Time’ (OVAT) approach to assess the effects of variations in selected factors particularly (development distance, saturation time, activation time of plate and mobile phase ratio) as graphical interpretation for robustness. The statistical insight was achieved with Multiple Linear Regression (MLR) and ANOVA. Results: The method was validated for precision, accuracy, detection limit and quantitation limit, and robustness. Conclusion: The method was successfully employed for the determination of apremilast from its in-house tablet formulation.

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应用Box-Behnken设计验证高效薄层色谱/密度法测定阿普米司特散装和内服片剂的稳健性

背景:Apremilast是磷酸二酯酶-4 (PDE-4)小分子抑制剂和免疫调节剂，用于治疗难治性银屑病关节炎。材料和方法:根据ICH指南，建立并验证了用于阿普雷米司特分析的高效薄层色谱(HPTLC)方法。以甲苯:甲醇(8:2 v/v)为流动相，在硅胶60f254薄层板上进行色谱分析。在230 nm处进行密度扫描时，观察到阿普雷米司特的致密斑点，Rf为0.64±0.05。校正图的线性回归分析结果显示r2 > 0.99，浓度范围为250 ~ 1500 ng/波段。采用“Box-Behnken设计”(BBD)和“响应面法”(RSM)的“实验设计”(DoE)作为传统的“一次一个变量”(OVAT)方法的进步进行了研究，以评估选定因素变化的影响，特别是(显影距离，饱和时间，平板活化时间和流动相比)作为鲁棒性的图形解释。通过多元线性回归(MLR)和方差分析(ANOVA)获得统计洞察力。结果:方法精密度、准确度、检出限、定量限、鲁棒性良好。结论:该法可用于阿普米司特自制片剂中阿普米司特的含量测定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Pharmaceutical Methods

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