PAT for tableting: inline monitoring of API and excipients via NIR spectroscopy.

This paper describes the application and implementation of inline NIR spectroscopy in an industrial tablet press. The content uniformity of a powder was analyzed via a NIR probe mounted on the feed frame. A PLS model with four latent variables (R(2)=0.97, Q(2)=0.95) was developed for the Active Pharmaceutical Ingredient (API) and two main excipients (EX1, EX2), according to the mixture DoE. The RMSEP corresponded to the relative errors of 2.7% for API, 1.7% for EX1 and 2.6% for EX2, compared to the nominal formulation. Transfer of the model, from the lab to an inline setup for manufacturing was achieved using local centering. There was a good agreement between the results of inline NIR and drawn tablets analyzed via UV-Vis. Notably, NIR indicated stochastic segregation behavior of the powder toward the end of the process, which was confirmed by the UV-Vis analysis. The outcome of our work was related to the recently published Ph. Eur. chapter 2.9.47 "Demonstration of uniformity of dosage units using large sample sizes".