Multipoint dissolution specification and acceptance sampling rule based on profile modeling and principal component analysis.

Abstract

In dissolution testing, multiple dissolution measurements at specific time points are needed in quality control when the compliance of the product requires controlled dissolution throughout the time course. The dissolution specification based on general multivariate confidence region was proposed by Chen and Tsong (8). This paper presents two alternative procedures when the dissolution profile consists of important measurements at more than 4 time points. In the first procedure, when the dissolution profile can be described by a physical curve through modeling, the dissolution specification is developed based on the confidence region of the parameters of the physical curve. In the second procedure, the principal components (PCS) as the linear combinations of the dissolution measurements are identified and dissolution specification is set based by the confidence intervals of the values of principal components. In both approaches the specification can be set at lower dimensions than the general multivariate confidence region approach. A single-stage acceptance rule can be used in both approaches by first projecting the dissolution values of each tablet in the new testing batch onto the determined parameters axes (through modeling in modeling approach and through projection on the selected PCS in principal component approach). Then check if the projections of the new tablet fall within the specifications. Finally, count the number of tablets that fall outside the specification limits and reject the batch if the proportion of out-of-specification tablet is high and accept the lot for release if the proportion is low.