Measurement uncertainty arising from sampling and analytical steps of dissolution test of glyburide tablets

Abstract

The dissolution test is an essential technique used in pharmaceutical research to assess the rate and extent of drug release from a dosage form into a dissolution medium. Accurate and reliable dissolution test results are crucial to ensure the quality and efficacy of the drug product. The aim of this study was to evaluate the measurement uncertainty arising from the sampling and analytical steps of the dissolution test for glyburide tablets. Dissolution test was performed using 900 mL of phosphate buffer pH 7.3 as dissolution medium and a dissolution apparatus equipped with paddles rotating at 75 rpm for 60 min. Quantification was performed by HPLC-UV. The uncertainty arising from sampling was estimated through classical Analysis of Variance (ANOVA), using 8-sampling targets, two samples for each sampling target and two replicas for each sample, totalizing 32 analyses. Uncertainty arising from analytical steps considered the uncertainty from dissolution step (estimated using Monte Carlo method and regression equation obtained using DoE) and uncertainty from quantification step. The overall uncertainty value was found to be 6.33 %. The sources of uncertainty contributing to the overall measurement uncertainty of the dissolution test were estimated to be 76.09 % from sampling, 22.15 % from the dissolution step, and 1.76 % from the quantification step. The study emphasizes the importance of evaluating measurement uncertainty in dissolution testing to ensure reliable and accurate drug product quality control. The results demonstrate that the dissolution test of glyburide tablets presented high sampling uncertainty and did not pass the dissolution test within the specified limits, probably due to glyburide’s low solubility. Univariate and multivariate rejection limits were calculated in order to ensure reduced particular and total producer’s risk, respectively. This study provides useful insights for pharmaceutical industries to optimize their quality control processes and ensure the efficacy and safety of their products.