In-line Blend Uniformity Monitoring Using Near-Infrared Spectroscopy as Process Analytical Technology (PAT) Tool
Barbara Schönfeld, Frank Theil, Sankaran Anantharaman, Matthias Degenhardt
AbbVie Germany Analytical R&D and Formulation Sciences, Ludwigshafen am Rhein
In the manufacture of solid dosage forms, the “uniformity of single-dose dosage forms” (Ph. Eur. 2.9.40) is a critical quality attribute in order to ensure the correct dosage of divided dosage forms such as tablets. In many cases, an important process to be evaluated in the development of the final dosage form directly linked to the aforementioned quality attribute is the blending process of powder blends – especially when the blending process represents the last process step before tableting.
The determination of the blend uniformity of a powder blend should therefore ideally be used to determine the homogeneity of the blend and thus lay the foundation for the dosing uniformity of the final dosage form. Conventionally the blend homogeneity is tested using the sample thieving method. Here a number of samples from the blend are obtained at certain positions in the blending container and tested for homogeneous active pharmaceutical ingredient content by HPLC. As this approach relies on off-line analytics, the results are generated with time delay with respect to the production step.
A more elegant approach is the in-line monitoring of blend uniformity with NIR. We here present our at AbbVie adapted approach of in-line blend uniformity using the SentroPAT NIR sensor (Sentronic). The blending endpoint is determined by an F-test using moving block standard deviation. The implementation of online data evaluation lead to a better understanding of the overall blending process, e.g. reduction of blending time or reduction of process steps.