Development and Validation of Reverse‐Phase High‐Performance Liquid Chromatography Method for Estimation of Itraconazole through Hydroxypropyl Methylcellulose Acetate Succinate based Polymeric Films using Quality by Design principles

Abstract

The present work encompasses the application of quality by design principles through the design of experiments for analytical method development using reverse‐phase high‐performance liquid chromatography for estimation of itraconazole as pure drug and from polymeric amorphous dispersion films. A three‐factor three‐level Box Behnken design was used for multivariate analysis of the critical method parameters namely mobile phase composition, flow rate, and pH with a target of achieving a faster retention time of less than 4 min. The optimized method conditions were mobile phase composition of acetonitrile:water in 70:30 ratio, a flow rate of 1 mL/min, and pH of water at pH 7.0. With these method conditions, a retention time of 3.7 min was achieved, and the method was successfully validated to establish linearity in the concentration range of 29.5–129.5 μg/mL with a correlation coefficient of 1.0. The limits of detection and quantification were 0.3 μg/mL and 1.0 μg/mL, respectively. Forced degradation study revealed the ability of the method to detect degradation to oxidation and acidic conditions. This method was used for estimation of drug assay and dissolution from polymeric solid dispersion films prepared at different drug loading concentrations with hydroxypropyl methyl cellulose acetate succinate for accessing formulation variables like polymer type and concentration for improved drug dissolution of Itraconazole.