Application of a mechanistic model of batch fluidized bed drying at laboratory and pilot scale

Abstract

The aim of this work was to test the feasibility of reducing experimentation during the development of the fluid bed drying process of a pharmaceutical product, by conducting experimentation at laboratory scale and by using a mechanistic model calibrated on the laboratory scale data to simulate the process at pilot scale. The advantage of this approach with respect to a fully empirical approach, is that a limited number of experiments are run at pilot scale with the purpose of scale verification, instead of an extensive experimental campaign. Batch fluidized bed drying experiments were run with two different formulations containing the same active pharmaceutical ingredient (API) at laboratory and pilot scales. A mechanistic model was calibrated at laboratory scale, and then the same parameters describing drying behavior were used in simulations of the drying process at the pilot scale. The setup of the model differed for the two formulations; in particular, for the more hygroscopic formulation, the model needs to account for a higher influence of the material on drying. The simulated product temperature and moisture content in granules were compared with experimental data. Model accuracy is good at steady state for granule moisture content and for product temperature, in particular for the more hygroscopic formulation. During dynamic phases the product temperature prediction is less accurate: this effect is more visible for the less hygroscopic formulation. Finally, the mechanistic model calibrated at laboratory scale was used to simulate experimental results obtained at pilot scale. Good agreement between simulations and experiments could be observed, confirming that the suggested approach could be used in order to considerably decrease experimental effort during process development with respect to a fully empirical approach.