Application of Box-Behnken Design and Response Surface Methodology for Selecting the Optimum RP-HPLC Conditions for the Simultaneous Determination of Paracetamol and Diclofenac Sodium Along With Three Skeletal Muscle Relaxants in Three Different Pharmaceutical Dosage Forms.

Abstract

An isocratic HPLC method has been developed and validated for estimating paracetamol and diclofenac sodium simultaneously with three skeletal muscle relaxants, namely, methocarbamol, tizanidine hydrochloride and chlorzoxazone in their pure standard mixtures and in different multi-component dosage forms in a single chromatographic run. HPLC separation was achieved on a C18 Inertsil ODS-3V 5μm column (250 × 4.6mm) using a mobile phase mixture containing acetonitrile and 25mM phosphate buffer (pH7.4 adjusted with NaOH) in the proportion of (39.7:60.3, v/v) pumped at 1.2mL/min flow rate with UV detection at 220nm. An experimental design was used by applying Plackett-Burman design for screening the most critical predictors affecting the chromatographic separation and Box-Behnken design for optimizing the selected predictors and creating the response surface between the selected predictors and the interested responses. ICH recommendations were applied for validating the proposed method with regard to linearity, precision, accuracy, selectivity, limits of detection and quantitation, and robustness. There are many applications for the optimized method that can be applied for routine estimation of the cited drugs in laboratories of quality control and pharmaceutical industries to save money and time and to reduce material waste and effort.