Mechanistic modeling of semicontinuous fluidized bed drying of pharmaceutical granules by incorporating single particle and bulk drying kinetics

Abstract

In this work, a mechanistic fluidized bed drying model computing the granule moisture content in function of granule size, drying time, process settings and formulation properties is developed. Modeling the moisture content distribution concerning the granule size is essential for tabletability and drug product quality. This work combines a mechanistic bulk model and a single-particle drying kinetics model in a semicontinuous mode. The added model complexity allows physical approximations of drying phenomena at both the drying system level and the granular level. This includes quantifying the variations in moisture content by taking into account the specific dryer design and the variations in granule size. The model performance was quantified through industrially relevant case studies. It was revealed that the proposed model structure accurately predicts the drying behavior of the yield fraction. However, systematic model biases were observed for the fine and coarse fractions of the granule size distribution. In addition, discrepancies in the predicted outgoing air properties (relative air humidity and air temperature) were obtained. Further enhancement of the model complexity, e.g. complete incorporation of fluidization and segregation phenomena, is likely to improve the model performance. Notwithstanding, the developed model forms a step towards a formulation-generic fluidized bed drying model as interacting mechanisms on different levels of the drying system are considered.

Keywords: Continuous manufacturing; Fluidized bed drying; Mathematical modeling; Twin-screw wet granulation.