Fonteyne, Margot2; Fussell, Andrew Luke3; Vercruysse, Jurgen4; Vervaet, Chris4; Remon, Jean Paul4; Strachan, Clare5; Rades, Thomas7; De Beer, Thomas6
1 Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet2 Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium. Electronic address: Margot.Fonteyne@Ugent.be.3 Optical Sciences group, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands.4 Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.5 Faculty of Pharmacy, Division of Pharmaceutical Technology, University of Helsinki, Finland.6 Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.7 Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet
According to the quality by design principle processes may not remain black-boxes and full process understanding is required. The granule size distribution of granules produced via twin screw granulation is often found to be bimodal. The aim of this study was to gain a better understanding of binder distribution within granules produced via twin screw granulation in order to investigate if an inhomogeneous spread of binder is causing this bimodal size distribution. Theophylline-lactose-polyvinylpyrrolidone K30 (PVP) (30-67.5-2.5%, w/w) was used as a model formulation. The intra-granular distribution of PVP was evaluated by means of hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy. For the evaluated formulation, no PVP rich zones were detected when applying a lateral spatial resolution of 0.5 μm, indicating that PVP is homogenously distributed within the granules.
International Journal of Pharmaceutics, 2014, Vol 462, Issue 1-2, p. 8-10