Department of Pharmaceutical Analysis

Ana Filipa Tavares da Silva


Laboratory of Pharmaceutical Process Analytical TechnologyAna Filipa Tavares da Silva

Ottergemsesteenweg 460
B-9000 Gent (Belgium)
Tel.: +32-9-264.83.55
Fax: +32-9-222.82.36
E-mail: Ana.TavaresdaSilva@UGent.be
Education: Pharmacist (Master in Pharmaceutical Sciences)

 

Statistical process monitoring of a continuous from powder-to-tablet manufacturing process based on wet granulation

The general aim of Ana Silva’s PhD is to develop a statistical process monitoring strategy for a fully continuous from-powder-to-tablet manufacturing line (Consigma™-25 system, GEA nv, Wommelgem, Belgium).

Conventional pharmaceutical manufacturing is generally accomplished using batch processing with off-line time-consuming and less efficient laboratory testing conducted on randomly collected samples to evaluate quality. Within the scope of increased process efficiency and production, there is the intention within the pharmaceutical industry to move from traditional batch processing to continuous processing. The introduction of this manufacturing model allows a substantial reduction of the production costs while increasing product quality and significantly reducing time-to-market. It also presents other benefits such as avoiding scale-up issues, increasing the processes’ stability and flexibility reducing product variability.

The Consigma™-25 continuous production line consists of four major units: a continuous twin screw high shear granulator (1), a six parallel cells fluid bed dryer (2), a granule conditioning unit (3) interfaced with a MODUL™ P tablet press. The system contains different interfaces at different locations where state-of-the-art process analyzers such as spectroscopic probes and particle size analyzers can be implemented. Numerous univariate process parameters are also continuously logged by the system itself in its different units during processing (temperatures, pressures, humidities, etc.), hence supplying a huge amount of data.

Ana Silva’s intention is to utilize multivariate data analysis tools to extract relevant process information from the generated datasets unveiling process trends (drifts) and existing correlations and cross-correlations between the logged variables (belonging to the same or to different units) in order to establish an online monitoring routine to ensure the optimal performance of the continuous line.

In reality, parts of the Consigma™-25 system operate in a semi-continuous manner. The granulator unit actuates continuously but afterwards the wet granules are transferred consecutively to different dryer cells and then, the material inside each cell can then be considered as a “mini-batch” and it will remain as such until its discharge and tableting. As the units in this continuous line perform either continuously or batch-wise a mixed approach utilizing both Multivariate Statistical Process Monitoring (MSPM) and Batch Statistical Process Monitoring (BSPM) is necessary. The concept of a mixed approach is an innovative solution never before described in literature and is a step forward in the direction of achieving an automated process monitoring strategy for these kind of systems.

Ana Silva is a joint PhD student of the Gent University and the University of Porto.

Her project is co-promoted by:

  • Prof. Thomas de Beer, Laboratory of Pharmaceutical PAT, Faculty of Pharmacy, Ghent University, Belgium
  • Dr. João Almeida Lopes, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto

Publications

  • Silva, A. F. T.; Burggraeve, A.; Denon, Q.; Van Der Meeren P.; Sandler, N.; Van Den Kerkhof, T.; Hellings, M.; Vervaet, C.; Remon, J. P.; Lopes, J. A.; De Beer, T. (2013) Particle sizing measurements in pharmaceutical applications: comparison of in-process methods versus offline methods. European Journal of Pharmaceutics and Biopharmaceutics, 85, 1006-1018.
  • Burggraeve, A.; Silva, A. F. T.; Van Den Kerkhof, T.; Hellings, M.; Vervaet, C.; Remon, J. P.; Vander Heyden, Y.; De Beer, T. (2012) Development of a fluid bed granulation control strategy based on real-time process and product measurements. Talanta, 100, 293–302.
  • Harasimowicz, J.; Marques, K. L.; Silva, A. F. T.; Costa, R. C. B. ; Prior, J. A. V.; Rodrigues, S. S. M. ; Santos, J. L. M. (2012) Chemiluminometric evaluation of melatonin and selected melatonin precursors' interaction with reactive oxygen and nitrogen species. Analytical Biochemistry, 420, 1-6.
  • Silva Ana F. T.; Marques Karine L.; Santos Joao L. M.; Lima J.L.F.C. (2011) Automatic Multi-pumping Flow System for the Chemiluminometric Screening of Scavenging Capacity against Singlet Oxygen. Analytical sciences, 27, 827-832.