Origin of profound changes in powder properties during wetting and nucleation stages of high-shear wet granulation of microcrystalline cellulose

Abstract The aim of this work was to understand the evolution of powder tabletability and flowability during wetting and nucleation stages of high-shear wet granulation (HSWG). Microcrystalline cellulose (MCC) was granulated with water using a high-shear process. Granule morphology, surface texture, size, porosity, specific surface area, tabletability, and flowability were characterized. MCC granulated with 5% water showed no change in tabletability but significantly improved flowability, corresponding to smoother surfaces and lower surface area. From 5% to 25% water, tabletability decreased by 1/4 but flowability remained unchanged. Granule shape and porosity remained unchanged while surfaces were smoothened, leading to decreased surface area. From 25% to 35% water, MCC granules became more round. There was another sharp decrease in tabletability but powder flowability remained unchanged. Forty-five percent of water led to more particle rounding and commencement of nucleation, which only slightly impacted tabletability and flowability. From 0% to 45% water, granule size decreased slightly and could not explain the significant changes in powder tabletability and flowability. Deteriorated tabletability was instead caused by surface smoothing, granule densification, and granule rounding. Enhanced powder flowability was caused mostly by surface smoothing with granule rounding as a minor contributor.

[1]  P. V. Danckwerts,et al.  GRANULE FORMATION BY THE AGGLOMERATION OF DAMP POWDERS PART I: THE MECHANISM OF GRANULE GROWTH , 1981 .

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

[3]  Pierre Guigon,et al.  Wet granulation in a batch high shear mixer , 2005 .

[4]  James D. Litster,et al.  Growth regime map for liquid-bound granules: further development and experimental validation , 2001 .

[5]  Changquan Calvin Sun,et al.  Reduced tabletability of roller compacted granules as a result of granule size enlargement. , 2006, Journal of pharmaceutical sciences.

[6]  A Study on the Effect of Wet Granulation on Microcrystalline Cellulose Particle Structure and Performance , 2006, Pharmaceutical Research.

[7]  Douglas W. Fuerstenau,et al.  Mechanisms of agglomerate growth in green pelletization , 1973 .

[8]  P. C. Knight.  Challenges in granulation technology , 2004 .

[9]  F. Ferrari,et al.  The surface roughness of lactose particles can be modulated by wet-smoothing using a high-shear mixer , 2004, AAPS PharmSciTech.

[10]  Lawrence X. Yu.  Pharmaceutical Quality by Design: Product and Process Development, Understanding, and Control , 2008, Pharmaceutical Research.

[11]  Marie-Elise Chateau,et al.  Processing a detergent powder formulation: Direct compression, and high shear wet granulation followed by compression , 2005 .

[12]  Changquan Calvin Sun,et al.  Influence of Crystal Structure on the Tableting Properties of Sulfamerazine Polymorphs , 2001, Pharmaceutical Research.

[13]  P. Heng,et al.  Effect of addition of water on the rheological and mechanical properties of microcrystalline celluloses , 1988 .

[14]  D. L. Gilbert,et al.  Effect of process parameters on compressibility of granulation manufactured in a high-shear mixer. , 2000, International journal of pharmaceutics.

[15]  D. Schulze.  Powders and Bulk Solids: Behavior, Characterization, Storage and Flow , 2021 .

[16]  Sarsvatkumar Patel,et al.  Understanding size enlargement and hardening of granules on tabletability of unlubricated granules prepared by dry granulation. , 2011, Journal of pharmaceutical sciences.

[17]  R. Censi,et al.  Physico-chemical and technological properties of sodium naproxen granules prepared in a high-shear mixer-granulator. , 2008, Journal of pharmaceutical sciences.

[18]  Changquan Calvin Sun,et al.  Roles of granule size in over-granulation during high shear wet granulation. , 2010, Journal of pharmaceutical sciences.

[19]  David Julian McClements,et al.  Food Emulsions: Principles, Practice, and Techniques , 1998 .

[20]  H W Frijlink,et al.  The effect of the amount of binder liquid on the granulation mechanisms and structure of microcrystalline cellulose granules prepared by high shear granulation. , 2005, International journal of pharmaceutics.

[21]  Changquan Calvin Sun,et al.  Quantifying effects of particulate properties on powder flow properties using a ring shear tester. , 2008, Journal of pharmaceutical sciences.

[22]  Michael J. Hounslow,et al.  DIRECT EVIDENCE OF HETEROGENEITY DURING HIGH-SHEAR GRANULATION , 2000 .

[23]  C. Nyström,et al.  Studies on direct compression of tablets. XXIII. The importance of surface roughness for the compactability of some directly compressible materials with different bonding and volume reduction properties , 1990 .

[24]  Changquan Calvin Sun,et al.  Improving Mechanical Properties of Caffeine and Methyl Gallate Crystals by Cocrystallization , 2008 .

[25]  B. Cuq,et al.  Flowability, cohesive, and granulation properties of wheat powders , 2008 .

[26]  Reactive binders in detergent granulation: Understanding the relationship between binder phase changes and granule growth under different conditions of relative humidity , 2008 .

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

[28]  M NewittD,et al.  A contribution to the theory and practice of granulation. , 1958 .

[29]  Sotiris E. Pratsinis,et al.  Agglomeration behaviour of powders in a Lödige mixer granulator , 1998 .

[30]  Kazutaka Kitagawa,et al.  Effect of Particle Shape on the Compaction and Flow Properties of Powders , 1989 .

[31]  K. Terada,et al.  The change in characteristics of microcrystalline cellulose during wet granulation using a high‐shear mixer , 2001, The Journal of pharmacy and pharmacology.

[32]  Changquan Calvin Sun.  Materials science tetrahedron--a useful tool for pharmaceutical research and development. , 2009, Journal of pharmaceutical sciences.

[33]  C. E. Capes,et al.  Particle size enlargement , 1980 .

[34]  B. J. Ennis,et al.  Nucleation, growth and breakage phenomena in agitated wet granulation processes: a review , 2001 .

[35]  Changquan Calvin Sun.  Setting the bar for powder flow properties in successful high speed tableting , 2010 .