(311b) Extension of a Mechanistic Model for Drying of Single Pharmaceutical Granules to Semi-Continuous Fluid Bed Drying

Ghijs, M., Ghent University
Mortier, S. T. F. C., Ghent University
Cappuyns, P., Janssen Pharmaceutica
Gernaey, K. V., Technical University of Denmark
De Beer, T., Ghent University
Nopens, I., Ghent University
A mechanistic model for predicting the drying behavior of a single pharmaceutical granule has been extended with a new mechanism. This extension led to improved model predictions for fluid bed drying. As this data indicated the average moisture content of a batch of granules instead of a single granule, the model application was further adjusted to the problem at hand.

In this work, the system under study is a ConsiGma-25â„¢ semi-continuous fluid bed dryer, which is continuously fed with wet granules coming from a twin-screw granulator through pneumatic transport. In the dryer unit, the continuous flow of granules is divided over its six separate drying segments, in which the granules are batch dried. This partitioning into parallel and sequential batch drying processes approaches a continuous mode over the entire dryer.

An exhaustive experimental campaign has already documented the influence of dryer cell load , air temperature and airflow on the drying curve of the granules, which were moreover classified into different size fractions (Ghijs et al., 2016).
Typically, two phases are distinguished during drying of wet porous particles: (1) a rapid first phase, where evaporation of the readily accessible water occurs, and (2) a slower second drying phase in which water from inside the granule migrates to the surface before it is evaporated. A mechanistic model which describes the two phase drying behavior of a single pharmaceutical granule was developed by Mortier et al. (2012).

However, an observation that could not be predicted with this model was that the decrease in moisture content stagnated as the moisture content decreased, until increasing the drying time did not further decrease the moisture content. This is attributed to the residual concentration of powder components dissolved in the remaining water, which in turn negatively impacts the partial vapor pressure of water in the air. Therefore, as the moisture content of the granules decreases, evaporation of water becomes increasingly hindered by the increasing concentration of the dissolved powder.

This phenomenon, described by the water activity coefficient which relates the partial vapor pressure of pure water to water in which a specific component is dissolved, was added to the drying model of Mortier et. al. Hence, a decrease in evaporation rate can now be predicted.


Mortier, S. T. F. C., De Beer, T., Gernaey, K. V., Vercruysse, J., Fonteyne, M., Remon, J. P., Vervaet, C., Nopens, I. (2012). Mechanistic modelling of the drying behaviour of single pharmaceutical granules. European Journal of Pharmaceutics and Biopharmaceutics, Vol. 80(3), 682–9.

Ghijs, M., De Leersnyder, F., Van Hauwermeiren, D., Vanhoorne, V., Vercruysse, J., Cappuyns, P., Mortier, S., et al. (2016). Model-based process analysis in continuous manufacturing of pharmaceuticals : calibration of a fluid bed dryer model. AIChE Conference proceedings : 2016 annual meeting. Presented at the 2016 AIChE Annual meeting, New York, NY, USA: American Institute of Chemical Engineers (AIChE).


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