Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets.

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect their processability and several critical quality attributes of the resulting granules and tablets.

[1]  J. Remon,et al.  The roller compaction of different types of lactose. , 1998 .

[2]  Hans Leuenberger,et al.  Batch And Continuous Processing In The Production Of Pharmaceutical Granules , 2003, Pharmaceutical development and technology.

[3]  T De Beer,et al.  Stability and repeatability of a continuous twin screw granulation and drying system. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[4]  J. Kushner,et al.  Examining the impact of excipient material property variation on drug product quality attributes: a quality-by-design study for a roller compacted, immediate release tablet. , 2011, Journal of pharmaceutical sciences.

[5]  I. Jones,et al.  In-line Size Monitoring of a Twin Screw Granulation Process Using High-Speed Imaging , 2013, Journal of Pharmaceutical Innovation.

[6]  Ingunn Tho,et al.  Multivariate analysis of relationships between material properties, process parameters and tablet tensile strength for alpha-lactose monohydrates. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[7]  J. Bonny,et al.  RELATION BETWEEN CRUSHING STRENGTH AND INTERNAL SPECIFIC SURFACE-AREA OF LACTOSE COMPACTS , 1989 .

[8]  James D. Litster,et al.  Twin screw wet granulation: Influence of formulation parameters on granule properties and growth behavior , 2013 .

[9]  The bulk volume changes of powders by granulation and compression with respect to capsule filling , 1996 .

[10]  P. Kleinebudde,et al.  Roll compaction/dry granulation: effect of raw material particle size on granule and tablet properties. , 2007, International journal of pharmaceutics.

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

[12]  Ingunn Tho,et al.  Comparative evaluation of the powder and compression properties of various grades and brands of microcrystalline cellulose by multivariate methods , 2009, Pharmaceutical development and technology.

[13]  Tormod Næs,et al.  Using raw material measurements in robust process optimization , 2001 .

[14]  H. Leuenberger,et al.  Investigation of compressibility and compactibility parameters of roller compacted Theophylline and its binary mixtures. , 2011, International journal of pharmaceutics.

[15]  Jean Paul Remon,et al.  Continuous granulation in the pharmaceutical industry , 2005 .

[16]  H. Vromans,et al.  Effects of high-shear granulation on granulate homogeneity. , 1999, Pharmaceutical development and technology.

[17]  Niklas Sandler,et al.  Prediction of quality attributes of continuously produced granules using complementary pat tools. , 2012, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[18]  J. S. Ard,et al.  Laser-raman spectra of lactose , 1974 .

[19]  John R. Grace,et al.  Biomass granular screw feeding: An experimental investigation , 2011 .

[20]  R. Pinal,et al.  Utility of Multivariate Analysis in Modeling the Effects of Raw Material Properties and Operating Parameters on Granule and Ribbon Properties Prepared in Roller Compaction , 2008 .

[21]  Jean Paul Remon,et al.  Effect of disintegrants on the properties of multiparticulate tablets comprising starch pellets and excipient granules. , 2012, International journal of pharmaceutics.

[22]  Thomas De Beer,et al.  Real-time assessment of critical quality attributes of a continuous granulation process , 2013, Pharmaceutical development and technology.

[23]  Juergen Werani,et al.  Semicontinuous granulation: the process of choice for the production of pharmaceutical granules? , 2004 .

[24]  T. Yoneyama,et al.  Correlation between loose density and compactibility of granules prepared by various granulation methods. , 2001, International journal of pharmaceutics.

[25]  H Leuenberger,et al.  New trends in the production of pharmaceutical granules: batch versus continuous processing. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[26]  Gintaras V. Reklaitis,et al.  Understanding critical material properties for solid dosage form design , 2006, Journal of Pharmaceutical Innovation.

[27]  H. Leuenberger,et al.  Roller compaction of different pseudopolymorphic forms of theophylline: Effect on compressibility and tablet properties. , 2010, International journal of pharmaceutics.

[28]  Michael J. Hounslow,et al.  Twin screw wet granulation: Granule properties , 2010 .

[29]  Lipika Chablani,et al.  Inline Real-Time Near-Infrared Granule Moisture Measurements of a Continuous Granulation–Drying–Milling Process , 2011, AAPS PharmSciTech.

[30]  Hans Leuenberger.  Scale-up in the 4th dimension in the field of granulation and drying or how to avoid classical scale-up , 2003 .

[31]  James J. Cartwright,et al.  Twin screw granulation: steps in granule growth. , 2012, International journal of pharmaceutics.

[32]  H Leuenberger,et al.  New trends in the production of pharmaceutical granules: the classical batch concept and the problem of scale-up. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[33]  N. Sandler,et al.  Prediction of granule packing and flow behavior based on particle size and shape analysis. , 2010, Journal of pharmaceutical sciences.

[34]  J. Trygg,et al.  A quality by design approach to investigate the effect of mannitol and dicalcium phosphate qualities on roll compaction. , 2013, International journal of pharmaceutics.

[35]  K. Zuurman,et al.  THE EFFECT OF DRY GRANULATION ON THE CONSOLIDATION AND COMPACTION OF CRYSTALLINE LACTOSE , 1993 .

[36]  H. Vromans,et al.  Relationship between inhomogeneity phenomena and granule growth mechanisms in a high-shear mixer. , 2002, International journal of pharmaceutics.

[37]  T De Beer,et al.  Continuous twin screw granulation: influence of process variables on granule and tablet quality. , 2012, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.