Uncertainty in dissolution test of drug release

Abstract

The uncertainty estimation of measurements in pharmaceutical manufacturing is often neglected in process optimization. For instance, tablet manufacturing consists of several process steps called unit operations where many measurements on the process conditions and quality are carried out. These measurements are assumed to be error-free and the possibility of the cumulative error throughout the process stages that only goes up has been ignored. Good manufacturing practices (GMP) guidelines provide regulations for the pharmaceutical industry on how to establish high quality production. However, they do not provide any instructions on pre-optimizing the process using a proper sampling scheme at each step. The uncertainty tests of measurements, for example in the tableting process, accounts for all significant sources of uncertainty in the production. In this study, the total error of the dissolution test according to the uncertainties described in the Pierre Gy's sampling theory has been studied. The present study shows that the overall uncertainty of the dissolution procedure could be clearly improved with optimization of the sampling chain.