466733 Continuous Wet Granulation in a Twin Screw Extruder: Effect of Process Variables on Residence Time Distribution and Granule Characteristics

Monday, November 14, 2016
Grand Ballroom B (Hilton San Francisco Union Square)
Shaza Darwish, Manuel Kuhs, Saeed Shirazian, Jacek Zeglinski, Ahmad Albadarin, Denise Croker and Gavin Walker, Bernal Institute, University of Limerick, Limerick City, Ireland

Wet granulation using a twin screw extruder is a promising continuous processing technique for granulation of pharmaceutical formulations. Although granulating with more consistency than a traditional high shear batch mixer,[1] the understanding of the granulation mechanisms in twin screw granulation is still not complete.[2] Furthermore, the residence time is very important, especially when multiple unit operations are connected in continuous processes.

Here we analyse the dependence of the residence time and granule size distribution (GSD) in a twin screw granulator on process parameters (screw speed, powder feed rate, liquid-to-solid ratio) and screw configuration (conveying, kneading, and cutting elements). The formulation was granulated in a 12 mm twin screw extruder (Three-Tec, Switzerland) with a length-to-diameter ratio of 40, using water as the granulating liquid. GSD was measured using a laser diffraction technique, while the residence time distribution was measured by adding a small dose of dye into the powder feeding port during steady state operation, followed by the sampling cup method described elsewhere.[3] Parameter values were chosen using a d-optimal factorial design to identify the most important parameters, and the results were rationalised to elucidate the granulation mechanisms in the different screw regions/screw elements.

[1] E.I. Keleb, A. Vermeire, C. Vervaet, J.P. Remon, Extrusion granulation and high shear granulation of different grades of lactose and highly dosed drugs: A comparative study, Drug Development and Industrial Pharmacy. 30 (2004) 679–691.

[2] M.R. Thompson, Twin screw granulation - review of current progress, Drug Development and Industrial Pharmacy. (2014) 1–9. doi:10.3109/03639045.2014.983931.

[3] A.S. El Hagrasy, J.R. Hennenkamp, M.D. Burke, J.J. Cartwright, J.D. Litster, Twin screw wet granulation: Influence of formulation parameters on granule properties and growth behavior, Powder Technology. 238 (2013) 108–115.


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See more of this Session: Poster Session: Pharmaceutical
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