Development of Stability Indicating TLC Densitometry Method of Edaravone Using QbD Approach: Degradation Kinetic Study

Abstract:

Objective: The objective of present method was to utilize risk based and systematic Quality by design approach for development of selective, sensitive, precise, accurate and robust stability-indicating TLC-densitometry for quantification of Edaravone and its degradation products. Method: The TLC-densitometric analysis was carried out in the absorbance mode at 244 nm using solvent system petroleum ether: ethyl acetate: glacial acetic acid (6ml:4ml:10μl v/v/v). This system was found to give compact and well resolved spot for Edaravone at an Rf value of 0.46 ± 0.21. Results: Edaravone undergoes significant degradation when subjected to stress degradation in acid, base, neutral, oxidative, photolytic, dry heat induced and accelerated humidity/temperature degradation conditions. The method was validated according to ICH guideline. Linearity was found in the range of 04-24 μg/band. The LOD and LOQ for Edaravone were 0.327μg/band and 0.989μg/band respectively. No interference was observed from excipients in formulation as well as degradation product, indicating specificity of the method. Moreover, the proposed method was also utilized to investigate the kinetics of acid, base, neutral and oxidative degradation process at different concentrations and temperatures. The kinetics of degradation profile was determined using linear and nonlinear regression analysis. The rate constants and half-life were calculated.

Key words: Edaravone, CNX approach, QbD, SIAMs, TLC-densitometry.