Valérie Vanhoorne

Valérie Vanhoornevalerie

Laboratory of Pharmaceutical Technology

Ottergemsesteenweg 460
B-9000 Gent (Belgium)
Tel.: +32-9-264.80.39
E-mail:
Education : Pharmacist

 

 

Innovative continuous manufacturing processes for production of oral solid dosage forms

Continuous production has some clear advantages over batch production as it offers flexibility and reduced variability in product quality, leads to reduced development time and costs, is suitable for process analytical technology and avoids scaling-up issues. Traditionally the pharmaceutical industry has been reluctant to switch from batch to continuous processes. However, mainly for economic reasons and improved product quality, pharmaceutical industry is moving towards continuous production.

Direct compression, the preferred manufacturing method for tablets, is not applicable for most powders, as they lack the appropriate flowability, compressibility and homogeneity. To improve these properties, agglomeration is applied, but mostly in batch. For the continuous production of tablets, continuous agglomeration techniques are necessary. Two continuous agglomeration processes are investigated in this Ph.D. thesis: crystal coating via spray drying and continuous granulation.

The aims of this Ph.D. are:

- Development of a continuous crystal coating method for improvement of flowability and tabletability of poorly compressible drugs. The manufacturing method is based on the introduction of dry powder particles into an atomized spray during spray drying.

- Development of a continuous manufacturing method for the production of δ-mannitol via spray drying and coprocessing of δ-mannitol and paracetamol via crystal coating.

- Investigate if the moisture induced polymorphic transition of δ- to β-mannitol which takes place during high shear granulation also takes place during twin screw granulation where the residence time is short, typically between 10-20 s.  The specific morphology of β-mannitol formed during granulation is associated with excellent compression properties due to a high specific surface area and a high plastic deformability.

- Development of a controlled release formulation with hydroxypropylmethylcellulose (HPMC) by continuous twin screw granulation using the ConsiGmaTM system (GEA Pharma Systems). Continuous twin screw granulation has proven to be an attractive method for the production of immediate release formulations. However, up-to-now, production and product quality of controlled release formulations manufactured using this innovative technology have not yet been evaluated. The influence of process (screw speed, throughput, liquid-to-solid-ratio, temperature) and formulation (viscosity HPMC, substitution degree HPMC, particle size drug, solubility filler) parameters on critical quality attributes is studied.

Publications

V. Vanhoorne, E. Peeters, B. Van Snick, J.P. Remon, C. Vervaet, Crystal coating via spray drying to improve powder tabletability, Eur. J. Pharm. Biopharm. 88 (2014) 939-944.

A. Kumar, J. Vercruysse, V. Vanhoorne, M. Toiviainen, P.E. Panouillot, M. Juuti, C. Vervaet, J.P. Remon, K.V. Gernaey, T. De Beer, I. Nopens, Conceptual framework for model-base analysis of residence time distribution in twin-screw granulation, Eur. J. Pharm. Sci. 71 (2015) 25-34.

 A.K. Kumar, J. Dhondt, F. De Leersnyder, J. Vercruysse, V. Vanhoorne, C. Vervaet, J.P. Remon, K.V. Gernaey, T. De Beer, I. Nopens, Evaluation of an in-line particle imaging tool for monitoring twin-screw granulation performance, Pow. Tech. 285 (2015) 80-87.

A. Kumar, J. Vercruysse, M. Toiviainen, P.E. Panouillot, M. Juuti, V. Vanhoorne, C. Vervaet, J.P. Remon, K. V. Gernaey, T. De Beer, I. Nopens, Mixing and transport during pharmaceutical twin-screw wet granulation: Experimental analysis via chemical imaging, Eur. J. Pharm. Biopharm. 87 (2014) 279-289.