Industrial application of heat- and mass balance model for fluid-bed granulation for technology transfer and design space exploration

• Published in: International journal of pharmaceutics: X Vol. 1; p. 100028
• Main Authors: Ochsenbein, David R., Billups, Matthew, Hong, Bingbing, Schäfer, Elisabeth, Marchut, Alexander J., Lyngberg, Olav K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2019; Elsevier
• Subjects: Digital twin; Fluid bed granulation; Heat- and mass balances; Industrial application; Mechanistic modeling; Technology transfer; Heat- and mass balances; Fluid bed granulation; Mechanistic modeling; Digital twin; Technology transfer; Industrial application
• ISSN: 2590-1567; 2590-1567
• DOI: 10.1016/j.ijpx.2019.100028

[Display omitted] This work demonstrates the application of state-of-the-art modeling techniques in pharmaceutical manufacturing for fluid bed granulation at varying scales to successfully predict process conditions and ultimately replace experiments during a technology transfer of five products. We describe a mathematical model able to simulate the time-dependent moisture profile in a fluid bed granulation process. The applicability of this model is then demonstrated by calibrating and validating it over a range of operating conditions, manufacturing scales, and formulations. The inherent capability of the moisture profile to serve as a simple, scale-independent surrogate is shown by the large number of successful scale-ups and transfers. A methodology to use this ‘digital twin’ to systematically explore the effects of uncertainty inherent in the process input and model parameter spaces and their impact on the process outputs is described. Two case studies exemplifying the utilization of the model in industrial practice to assess process robustness are provided. Lastly, a pathway to leverage model results to establish proven acceptable ranges for individual parameters is outlined.