A hybrid model for multipoint real time potency observation in continuous direct compression manufacturing operations.

The ongoing transition from batch to continuous manufacturing offers both challenges and opportunities in the field of oral solid dosage form production. In turn, Process Analytical Technology (PAT) offers a path towards the successful deployment of continuous tablet manufacturing in rotary tablet presses. One promising PAT tool for this endeavour is the NIR-derived potency measurement. However, the high degree of noise in the data may hamper the extraction of useful information. For this reason, this work focused on the implementation of an adaptive Kalman filter algorithm that incorporates and reconciles the potency prediction given by one or more NIR probes with those of a semi-mechanistic compartmental model developed for the application at hand. This approach allowed for more robust concentration estimations. Furthermore, it was observed that potency levels in multiple locations in the studied tablet press (including those in the finished tablets) could be appropriately inferred using a single in-line measurement data stream. This methodology thus opens the door to advanced process control applications.

Numerical Validation of a Population Balance Model Describing Cement Paste Rheology.

Rheology control is essential during the period in which cement and concrete pastes are encountered in the fresh state, due to the fact that it directly affects workability, initial placement and the structural performance of the hardened material. Optimizations of clinker formulations and reductions in cement-to-water ratios induced by economic and environmental considerations have a significant effect in rheology, which invokes the need for mechanistic models capable of describing the effect of multiple relevant phenomena on the observed paste flow. In this work, the population balance framework was implemented to develop a model able to relate the transient microstructural evolution of cement pastes under typical experimental conditions with its macroscopic rheological responses. Numerical details and performance are assessed and discussed. It was found that the model is capable of reproducing experimentally observed flow curves by using measured cluster size distribution information. It is also able to predict the complex rheological characteristics typically found in cement pastes. Furthermore, a spatially resolved scheme was proposed to investigate the nature of flow inside a parallel-plates rheometer geometry with the objective of assessing the ability of the model of qualitatively predicting experimentally observed behavior and to gain insight into the effect of possible secondary flows.