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

Dissolution is used to determine the rate and extent of drug release from the dosage form into a dissolution medium, which allow to assess the batch-to-batch variability. Considering that the dissolution test is used to predict the vivo performance of the drug as well, it is important to guarantee the quality and reliability of dissolution test results. The aim of this work was to evaluate the measurement uncertainty arising from sampling and analytical steps of dissolution test of prednisone tablets. Dissolution test was performed using 900 mL of purified water as dissolution medium and a dissolution apparatus equipped with paddles rotating at 50 rpm for 30 min. Quantification was performed by UV spectrophotometer. Uncertainty arising from sampling was estimated using the duplicate method (empirical approach), using 17-sampling target, two samples for each sampling target, and three replicas for each sample, totalizing 102 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. Overall uncertainty value was found to be 2.2%, which is below the target uncertainty value (ut =2.5%). The contributions of uncertainty sources in this study were as follows: 24% from sampling uncertainty, 29% from the dissolution step uncertainty, and 47% from the quantification step uncertainty. The results of dissolution test should be compared to the specification limits (Q). According to the pharmacopeia requirements, the batch of the medicine should be declared compliant if the dissolved amount of prednisone for six tablets are above the specification limits + 5% (Q+5%=85%). Since the measured values for all six tablets (96.5%, 94.0%, 96,4%, 95.3%, 96.0%, and 96.9%) were above the multivariate acceptance limit (90.2%, calculate as the standard uncertainty multiplied by multivariate coverage factor), the batch of the prednisone tablets was declared complaint, with a reduced total risk of false decision (total risk value below 5%).

Measurement Uncertainty and Conformity Assessment Applied to Drug and Medicine Analyses - A Review.

Analytical results are often used in scientific research, industrial and clinical applications to support decision making. Despite all efforts to ensure the reliability of analytical results (including method validation, internal quality control, use of certified reference materials, proficiency tests, and ISO 17025 accreditation), there will always be an uncertainty associated with the measured value. The measurement uncertainty expresses the quality of the analytical result and allows the comparability between analytical results or between the measured value and the specification limit(s). This work discusses the importance of measurement uncertainty, including the steps involved in the measurement uncertainty evaluation, the bottom-up and top-down approaches used in measurement uncertainty calculation, the measurement uncertainty evaluation in drug and medicine analyses, and the application of measurement uncertainty in conformity assessment for quality control, stability studies, and pharmaceutical equivalence.