QbD-Driven Development and Validation of a HPLC Method for Estimation of Tamoxifen Citrate with Improved Performance.

Abstract

The current studies entail Quality by Design (QbD)-enabled development of a simple, rapid, sensitive and cost-effective high-performance liquid chromatographic method for estimation of tamoxifen citrate (TMx). The factor screening studies were performed using a 7-factor 8-run Taguchi design. Systematic optimization was performed employing Box-Behnken design by selecting the mobile phase ratio, buffer pH and oven temperature as the critical method parameters (CMPs) identified from screening studies, thus evaluating the critical analytical attributes (CAAs), namely, peak area, retention time, theoretical plates and peak tailing as the parameters of method robustness. The optimal chromatographic separation was achieved using acetonitrile and phosphate buffer (pH 3.5) 52:48 v/v as the mobile phase with a flow rate 0.7 mL/min, an oven temperature 40°C and UV detection at 256 nm. The method was validated as per the ICH recommended conditions, which revealed high degree of linearity, accuracy, precision, sensitivity and robustness over the existing liquid chromatographic methods of the drug. Also the method was applied for the estimation of TMx in nanostructured formulations, which indicated no significant change in the retention time. In a nutshell, the studies demonstrated successful development of the HPLC method of TMx with improved understanding of the relationship among the influential variables for enhancing the method performance.