Development and validation of RP-HPLC method for pitavastatin calcium in bulk and formulation using experimental design

ABSTRACT

The optimization of HPLC method involves several variables whose influence has been widely studied. However, inmost of the cases, only process variables are taken into account. In this work, the influence of mixture compositionon peak quality parameters of Pitavastatin calcium in bulk and tablet dosage form has been studied using a mixturesimplex design. A simplex centroid design with axial points in a pseudo-component representation was generated fromthe pure mixture components. Twelve ternary mixture mobile phases corresponding to augmented design points weretested to separate the drug in sample. The statistical analysis was performed to generate the polynomial equation foreach response. The desirability approach was used to determine the optimal mobile phase composition. Furthermore,the method was validated as per the ICH guidelines using specificity, linearity, accuracy, precision, sensitivity, systemsuitability, and robustness. The results of experimental design were statistically tested for full and in portion to getbest fitted model which accurately describe changes in the proportion of these solvents in the mobile phase close to theregion of optimal peak quality. The method demonstrated optimum chromatographic separation with isocratic elutionof the mobile phase containing a mixture of acetonitrile-water (pH 3.0)-tetrahydrofuran (435502, v/v/v) with a flowrate at 1.0 ml/minute. Design of experiment optimization strategy is a powerful tool to acquire the maximum qualitydata while performing minimum number of experiments. The mobile phase composition was successfully optimizedusing simplex centroid mixture design with desirability approach. Additionally, developed method can be appliedfor routine quantitative analysis of Pitavastatin calcium in bulk and tablet dosage form as it was found to be simple,sensitive, and robust.