(642e) Validation of Combined PBM-RTD Technique to Simulate Continuous Wet Granulation Systems for Pharmaceutical Manufacturing Processes

Wet granulation is a key unit operation in the pharmaceutical industry employed in the production of solid oral dosage formulations through the continuous manufacturing route. In an effort to predict the outlet compositions of the particles of a continuous granulator, the study of residence time distributions (RTDs) is crucial in order to predict the effects of variabilities in the inlet parameters such as feeder fluctuations and blend inhomogeneity on the outlet granule particle sizes and compositions. Population Balance Models (PBMs) are developed and extensively employed in modeling wet granulation systems in order to track the particle size distributions (PSDs) and porosities of the particles [1].

An initial experimental study on a twin screw granulator was performed using a low API dose blend across a DOE consisting of variation in powder feed rate, liquid content and screw rotation speed. The RTD pulse experiments were carried out on the DOE and exit concentration was measured in real time using an inline near infrared probe (NIR). The residence time profile was fitted to a theoretical model consisting of tank-in-series, plug flow fractions, parallel streams, etc. Moreover, empirical mathematical correlations were obtained for the mean residence time (MRT) with respect to the operating DOE conditions. These studies and results were in line with previously published results in literature [2, 3].

A granulation PBM with RTD mechanics incorporated to it would track the flow of key species such as API thereby quantifying the processes and attributes of the outlet granules completely. The model would provide the researcher with the potency of the API across granule sizes. The goal of this proposed study would be to experimentally validate the developed models. The results of the study would help in developing real-time control strategies that would ensure granules with critical quality attributes (CQAs) consistent over time during the production of the granules.

[1] A. Chaudhury, ‘Mechanistic modeling, simulation and optimization of wet granulation processes’, Rutgers University - Graduate School - New Brunswick, 2015.

[2] A. Kumar et al., ‘Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation’, European Journal of Pharmaceutical Sciences, vol. 71, pp. 25–34, Apr. 2015.

[3] H. Y. Ismail, M. Singh, S. Darwish, M. Kuhs, S. Shirazian, D. M. Croker, M. Khraisheh, A. B. Albadarin, and G. M. Walker, ‘Developing ann-kriging hybrid model based on process parameters for prediction of mean residence time distribution in twin-screw wet granulation,’ Powder Technology, vol. 343, pp. 568-577, 2019.