International Journal of Pharmaceutics 290 (2005) 129–136 The effect of the amount of binder liquid on the granulation mechanisms and structure of microcrystalline cellulose granules prepared by high shear granulation A.M. Bouwman a,∗ , M.J. Henstra a , D. Westerman b , J.T. Chung b , Z. Zhang b , A. Ingram b , J.P.K. Seville b , H.W. Frijlink a a Department of Pharmaceutical Technology & Biopharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands b Centre for Formulation Engineering, Department of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK Received 20 July 2004; received in revised form 12 November 2004; accepted 23 November 2004 Abstract The structure of granules changes during the high shear granulation process. The purpose of this research was to investigate the effect of the amount of binder liquid on the structure of the granules and the structural changes which occur during the granulation process, using microcrystalline cellulose (MCC) and water as the model system. The structure is the result of the granulation mechanism; therefore, conclusions can be drawn about the latter by studying the former. X-ray microtomography and scanning electron microscopy (SEM) were applied in order to visualise the densification process of granules, which were first freeze dried in order to preserve their structure. Variations in their porosity were quantified by applying image analysis to the tomography results. In order to link the granule mechanical properties to their structural differences, a micromanipulation technique was used to measure granule resistance to deformation. MCC granules granulated with 100% (w/w) water showed increased densification with time, as expected; detailed examination showed that densification is more pronounced in the core of the granule; whereas the outer part remained more porous. Increased densification reduces deformability, so that granules become more resistant to breakage. The lower deformability of the densified granules in the final stages of granulation might result in establishment of equilibrium between attrition and growth, without substantial gross breakage. On the other hand, when more water was used (125%, w/w), densification was hardly observed; the porosity of the granule core was still high even after prolonged granulation times. This may be explained by the fact that higher water content increases the ease of deformation of granules. This increased deformability led to significant granule breakage even during the final phases of the granulation process. Therefore, for these granules a final equilibrium between breakage and coalescence might be established. This also explains why more granules produced with 125% granulation liquid were composed of fragments of irregular shape. ∗ Corresponding author. Tel.: +31 50 363 23 97; fax: +31 50 363 25 00. E-mail address: a.bouwman@farm.rug.nl (A.M. Bouwman). 0378-5173/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2004.11.024