title: Transfer from high-shear batch to continuous twin screw wet granulation: a case study in understanding the relationship between process parameters and product quality attributes.
abstract: A twin screw to high-shear batch granulation technology switch was evaluated for a pharmaceutical development project. Differences in granule (particle size distribution and porosity) and tablet (dissolution) quality attributes were analysed for both continuous and batch technologies. Liquid to solid (L/S) ratio, screw configuration and screw speed parameters on the twin screw granulator were varied, with output granule and tablet properties characterised. L/S and screw configuration were found to influence the granule particle size distribution, porosity and tablet dissolution. At 0.15 L/S, the particle size distribution showed a significant proportion of ungranulated material in the output granule. As the L/S is increased, the level of ungranulated material decreased. An increase in L/S and the number of kneader elements caused a decrease in granule porosity and tablet dissolution. Twin screw and batch granulation technologies generated different granule properties (size and shape) at a constant L/S. A lower L/S in twin screw granulation was needed to achieve similar tablet attributes. It is concluded that differences in liquid addition and therefore initial granule nucleation caused differences in granule properties, which impacted tablet attributes and manufacturability.
authors.affiliation: Pharmaceutical Development, AstraZeneca, Macclesfield, Cheshire, SK10 2NA, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Beer
authors.forename: David
authors.initials: D
authors.lastname: Wilson
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Huang
authors.forename: Marcel
authors.initials: M
authors.lastname: De Matas
mesh_terms: D002626:Chemistry, Pharmaceutical; D010316:Particle Size
keywords: compression; continuous wet granulation; factorial design; formulation; high shear granulation; image analysis; principle component analysis; processing; quality attributes; twin screw granulation