Central Composite Design Assisted HPLC Method Development for High-Throughput Analysis of Telmisartan, Chlorthalidone and Metoprolol Succinate

Optimization for the estimation of drug combinations by HPLC is essential and superior in terms of efficient, cost, accuracy and regulatory compliance comparing normal method development making it high quality pharmaceutical analysis. Optimization by Central Composite Design is highly significant due to its advanced and systematic approach of multiple variables evaluation and their interaction providing minimal number of experimental runs by giving an accurate mathematical models like Response surface method which predicts method performance under various conditions. The present study uses Telmisartan, Chlorthalidone and Metoprolol Succinate. In their combined tablet dosage forms for method development and validation using CCD as an Optimization tool by HPLC. For Optimization, acetonitrile concentration as mobile phase, pH of the phosphate buffer and flow rate were selected as factors with chosen responses from capacity factor, retention time and resolution between the peaks. The results obtained from CCD experiments were presented as perturbation and response surface plots to get visual representation of individual and multiple factors. Overall the method gets a desirability value of 0.770 indicating best method performance. Retention time of Telmisartan, Chlorthalidone and Metoprolol Succinate. were 5.239, 7.692 and 10.623 minutes using acetonitrile and 0.05M phosphate buffer in the ratio 30:70 %V/V and pH of 6.2 at a flow rate 1.0 ml/min at a detection wavelength of 215 nm. Validation parameters according to ICH guidelines were done and found to be within limits. The method may be adopted for routine analysis of these drug in pharmaceutical industry.