Analytical Quality-by-Design Approach for the Stability Study of Thiocolchicoside by Eco-Friendly Chromatographic Method

摘要

A robust and eco-friendly stability-indicating high-performance thin-layer chromatography (HPTLC) method was developed for the stability study of thiocolchicoside using analytical quality-by-design approach. Full factorial design was used for screening potential variables affecting method development. Box-Behnken design was used subsequently for investigation of the main, interactive, and quadratic effects of these variables on response. Four potential variables were selected on the basis of scientific knowledge for the development of a method for the stability study of thiocolchicoside. The selected potential factors, namely, volume of water (mL), saturation time (min), migration distance (mm), and volume of mobile phase (mL) were screened by 2(4) full factorial designs by selecting resolution as a critical method attribute. Pareto chart analysis showed that 3 variables, namely, volume of water (mL), saturation time (mm), and migration distance (mm), out of 4 potential variables were significantly affecting the response variable (resolution). Optimization with response surface methodology further clarified the relationship between critical variables and resolution using Box-Behnken design. The experimental design model was found to be quadratic, and the design space was developed on the basis of suggested model for optimization of critical method variables for maximum desirable resolution and for the development of a control strategy of the HPTLC method for the stability study of thiocolchicoside. The developed method was validated for linearity, range, specificity, precision, accuracy, limit of detection and limit of quantification as per the International Conference on Harmonization guidelines (ICH) Q2 (R1). The developed method was applied for the estimation of thiocolchicoside in its pharmaceutical dosage forms. The degradation products formed in acidic and alkaline media were isolated and characterized by their infrared (IR), nuclear magnetic resonance (NMR), and mass spectral data.