Department of Pharmaceutical Analysis

Dr. Séverine Mortier

BIOMATH, Model-based analysis and optimisation of (bio)processes
Department of Mathematical Modelling, Statistics and BioinformaticsSeverine Mortier

Coupure Links 653
B-9000 Gent (Belgium)
Tel.:  +32-9-264.61.96
Fax. :  +32-9-264.62.20
E-mail: Severine.Mortier@UGent.be
Education: Bio-engineer

Obtained degree of Doctor in Applied Biological Sciences in 2014

Modelling of a drying process in a continuous pharmaceutical production line

Nowadays, the pharmaceutical industry relies mostly on batch processing. However, this production method has several disadvantages: upscaling from lab or pilot to production scale is not straightforward, lack of process understanding, limited control of essential process variables… The shift to a continuous process with more in-process monitoring and control, which would make the process easier to operate and more cost-effective, has for a long time been hindered by the regulatory uncertainty, i.e. the vision of the regulatory authorities on such innovative production methods was unclear. That has all changed with the publication of the PAT guidance in 2004.

In order to control the quality of the final product, advanced quality control systems should be implemented. These control systems should rely on in-line measurements and real-time adjustment of the most significant process variables. However detailed knowledge of the process and the effect of essential process variables on the product quality is required to develop these control systems. When mapping the available process knowledge, the behavior of the raw materials during processing can be modeled using a mechanistic modeling approach. Once such a mechanistic model has been established, it has to be validated by several experiments.

The validated mechanistic models help to gain insight in the process, and can be used to simulate the process for a range of settings of the different process inputs. These simulations can predict the outcome of the process, and thereby help to map and interpret the influence of changing input variables on the final product quality.

This research project focuses on a continuous pharmaceutical tablet production process (Consigma, GEA) , and more specifically on the drying of the wet granules that are produced by a continuous granulator. The goal is to develop a combined CFD-PBM model to describe the drying process in a fluid bed dryer, and to achieve an online and real time adaptation of the drying process on the basis of the available process measurements. CFD is a mathematical tool to study the flow pattern of the granules in the gas phase, whereas a PBM-approach is interesting for the description of the change of the moisture content of the granules during the drying process.

This project is co-promoted by:

  • Prof. Dr. Thomas De Beer, Laboratory of Pharmaceutical PAT, Faculty of Pharmacy, Ghent University, Belgium
  • Prof. Dr. Ingmar Nopens, BIOMATH, Faculty of Bioscience Engineering, Ghent University, Belgium
  • Prof. Dr. Krist Gernaey, Department of Chemical and Biochemical Engineering Process Engineering and Technology, Technical University of Denmark, Lyngby, Denmark

Publications

  • Mortier, S.T.F.C.; Van Hoey, S.; Cierkens, K.; Gernaey, K.V.; De Baets, B.; Seuntjes, P.; Nopens, I.; De Beer, T. (2013). A GLUE uncertainty analysis of a drying model of pharmaceutical granules. European Journal of Pharmaceutics and Biopharmaceutics, 85, 984-995.
  • Mortier, S.T.F.C.; Gernaey, K.V.; De Beer, T.; Nopens, I. (2013) Development of a Population Balance Model of a pharmaceutical drying process and testing of solution methods. Computers & Chemical Engineering, 50, 39-53.
  • Mortier, S.T.F.C.; Van Daele, T.; Gernaey, K.V.; De Beer, T.; Nopens, I. (2012) Reduction of a single granule drying model: An essential step in preparation of a PBM with a continuous growth term. AIChE Journal, 59, 1127-1138.
  • Mortier, S.T.; 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, 80, 682-689.
  • Mortier, S.T.; De Beer, T.; Gernaey, K.V.; Remon, J.P.; Vervaet, C.; Nopens, I. (2011) Mechanistic modelling of fluidized bed drying processes of wet porous granules: A review. European Journal of Pharmaceutics and Biopharmaceutics, 79, 205-225.