QbD-Driven Central Composite Design in Dual Analytical Method Development: Simultaneous Estimation of Olanzapine and Samidorphan by HPLC and HPTLC

The current study represents the development and validation of HPLC and HPTLC methods for the simultaneous estimation of Olanzapine and Samidorphan in their combined formulation by using the design of experiments (DoE). In the RP-HPLC method, three independent factors, like Organic solvent composition, flow rate, and wavelength, were employed. HPTLC method factors like developing distance, Chamber saturation time, and methanol content in the mobile phase. Central composite design (CCD) was applied and also to study the response surface methodology. Capacity factor, Retention time, and Resolution were simultaneously optimized by using the Desirability function for the HPLC method and the Rf value for both drugs as responses in the HPTLC method. The proposed RP-HPLC method, the optimized and predicted data consisted of mobile phase acetonitrile: phosphate buffer (pH 6.8 with 1ml orthophosphoric acid) in the ratio of 45: 55%v/v respectively, at a flow rate of 0.8 ml/min and wavelength of 261 nm. By applying these optimum conditions with the Solar C18 column baseline partition of both drugs had good resolution and run time of 4.623 min for olanzapine and 7.767 min for Samidrophan. In HPTLC, separations were performed on silica gel 60 F254 using acetonitrile: glacial acetic acid: methanol (5: 4.5: 0.5%v/v/v) as mobile phase. The Rf value was found to be 0.48 for Olanzapine and 0.87 Samidrophan were scanned at 236 nm. Both methods optimized conditions were validated according to International Council for Harmonization guidelines (ICH). The proposed methods can be routinely employed in quality control for the analysis of Olanzapine and Samidorphan in the pharmaceutical dosage forms.