Influence of fill factor variation in high shear granulation on the post granulation processes: Compression and tablet properties

Abstract This paper describes an investigation of the effect of fill factor; on the compaction behaviour of the granules during tabletting and hence mechanical properties of tablets formed. The fill factor; which is the ratio of volume of wet powder material to vessel volume of the granulator, was used as an indicator of batch size. It has been established previously that in high shear granulation the batch size influences the size distribution and granule mechanical properties [1]. The work reported in this paper is an extension to the work presented in [1], hence granules from the same batches were used in production of tablets. The same tabletting conditions were employed during tabletting to allow a comparison of their properties. The compaction properties of the granules are inferred from the data generated during the tabletting process. The tablet strength and dissolution properties of the tablets were also measured. The results obtained show that the granule batch size affects the strength and dissolution of the tablets formed. The tablets produced from large batches were found to be weaker and had a faster dissolution rate. The fill factor was also found to affect the tablet to tablet variation of a non-functional active pharmaceutical ingredient included in the feed powder. Tablets produced from larger batches show greater variation compared to those from smaller batches.

[1]  J. Sousa,et al.  Compaction, compression and drug release characteristics of xanthan gum pellets of different compositions. , 2004, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[2]  Xinyuan Shi,et al.  Visualizing excipient composition and homogeneity of Compound Liquorice Tablets by near-infrared chemical imaging. , 2012, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[3]  Alvin W. Nienow,et al.  Particle growth mechanisms in fluidised bed granulation—I: The effect of process variables , 1983 .

[4]  Paul R. Mort,et al.  Scale-up of binder agglomeration processes , 2005 .

[5]  Stephen J. Allen,et al.  Development of a value-added soil conditioner from high shear co-granulation of organic waste and limestone powder , 2014 .

[6]  D. Bernache-Assollant,et al.  Use of cycles of compression to characterize the behaviour of apatitic phosphate powders , 2002 .

[7]  T K Bock,et al.  Experience with the Diosna mini-granulator and assessment of process scalability. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[8]  L. Chan,et al.  Effects of process variables and their interactions on melt pelletization in a high shear mixer , 2000 .

[9]  Ahmad B. Albadarin,et al.  Alternative method for producing organic fertiliser from anaerobic digestion liquor and limestone powder: High Shear wet granulation , 2013 .

[10]  Paul R. Mort,et al.  Scale-up and control of binder agglomeration processes : Flow and stress fields , 2009 .

[11]  P Kleinebudde,et al.  Melt pelletisation of a hygroscopic drug in a high shear mixer. Part 1. Influence of process variables. , 1999, International journal of pharmaceutics.

[12]  Gavin K. Reynolds,et al.  Blade–granule bed stress in a cylindrical high shear granulator: I—Online measurement and characterisation , 2013 .

[13]  José Manuel Amigo,et al.  Fast assessment of the surface distribution of API and excipients in tablets using NIR-hyperspectral imaging. , 2011, International journal of pharmaceutics.

[14]  Anders Rasmuson,et al.  A volume-based multi-dimensional population balance approach for modelling high shear granulation , 2006 .

[15]  O. Mondain-Monval,et al.  From compressibility to structural investigation of sodium dodecyl sulphate — Part 1: Powder and tablet physico-chemical characteristics , 2007 .

[16]  Peter York,et al.  The effect of batch size on scale-up of a pharmaceutical granulation in a fixed bowl mixer granulator , 1996 .

[17]  M. Blanco,et al.  Content uniformity studies in tablets by NIR-CI. , 2011, Journal of pharmaceutical and biomedical analysis.

[18]  Erwin Adams,et al.  Scaling-up of a lactose wet granulation process in Mi-Pro high shear mixers. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[19]  D. Vojnovic,et al.  Melt granulation in a high shear mixer: optimization of mixture and process variables using a combined experimental design , 1999 .

[20]  Ragnar Ek,et al.  Compression behaviour and compactability of microcrystalline cellulose pellets in relationship to their pore structure and mechanical properties , 1995 .

[21]  M. Adams,et al.  Effect of batch size on mechanical properties of granules in high shear granulation , 2011 .

[22]  M. Adams,et al.  An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment. , 2012, International journal of pharmaceutics.

[23]  Ahmad B. Albadarin,et al.  Optimisation of high shear granulation of multicomponent fertiliser using response surface methodology , 2011 .

[24]  W. Skinner,et al.  Agglomeration behaviour and product structure of clay and oxide minerals , 2013 .

[25]  G. Marosi,et al.  Raman microscopic evaluation of technology dependent structural differences in tablets containing imipramine model drug. , 2010, Journal of pharmaceutical and biomedical analysis.

[26]  Keijiro Terashita,et al.  Optimization of operating conditions in a high-shear mixer using dem model: determination of optimal fill level. , 2002, Chemical & pharmaceutical bulletin.

[27]  I. Antal,et al.  Investigation on drug dissolution and particle characteristics of pellets related to manufacturing process variables of high-shear granulation. , 2006, Journal of biochemical and biophysical methods.

[28]  M. Viana,et al.  Powder Functionality Test: A Methodology for Rheological and Mechanical Characterization , 2005, Pharmaceutical development and technology.

[29]  David Parker,et al.  A phenomenological study of a batch mixer using a positron camera , 1993 .

[30]  O. Mondain-Monval,et al.  From compressibility to structural investigation of sodium dodecyl sulphate — Part 2: A singular behavior under pressure , 2007 .

[31]  B. H. Ng,et al.  Effect of granulation scale-up on the strength of granules , 2009 .

[32]  J. Newton,et al.  Determination of tablet strength by the diametral-compression test. , 1970, Journal of pharmaceutical sciences.

[33]  Michael J. Hounslow,et al.  Effect of impeller speed on mechanical and dissolution properties of high-shear granules , 2010 .

[34]  Jpk Seville,et al.  Agglomerate strength measurement using a uniaxial confined compression test , 1994 .

[35]  Ahmad B. Albadarin,et al.  The variability in nutrient composition of Anaerobic Digestate granules produced from high shear granulation. , 2013, Waste management.

[36]  H. Kristensen,et al.  Melt pelletization in a high shear mixer. IV. Effects of process variables in a laboratory scale mixer , 1993 .

[37]  Henderik W Frijlink,et al.  Application of process analytical technology in tablet process development using NIR spectroscopy: blend uniformity, content uniformity and coating thickness measurements. , 2008, International journal of pharmaceutics.

[38]  S. Biggs,et al.  Advancing contact angle of iron ores as a function of their hematite and goethite content: Implications for pelletising and sintering , 2004 .

[39]  Nejat Rahmanian,et al.  Effect of scale of operation on granule strength in high shear granulators , 2008 .

[40]  Peter York,et al.  Scale-up of a pharmaceutical granulation in fixed bowl mixer-granulators , 1996 .