Simple assessment of homogeneity in pharmaceutical mixing processes using a near-infrared reflectance probe and control charts.

Determination of homogeneous mixing of the active pharmaceutical ingredient (API) is an important in-process control within the manufacturing of solid dosage forms. In this paper two new near-infrared (NIR) based methods were presented; a qualitative and a quantitative method. Both methods are based on the calculation of net analyte signal (NAS) models which were very easy to develop, specific with respect to the API and required no additional reference analysis. Using a well-mixed batch as a 'golden standard' batch, control charts were developed and used for monitoring the homogeneity of other batches with NIR. The methods were fast, easy to use, non-destructive and provided statistical tests of homogeneity. A mixing study was characterized with the two methods and the methods were validated by comparison with traditional HPLC analysis.