title: Statistical analysis and comparison of a continuous high shear granulator with a twin screw granulator: Effect of process parameters on critical granule attributes and granulation mechanisms.
abstract: This study is concerned with identifying the design space of two different continuous granulators and their respective granulation mechanisms. Performance of a continuous high shear granulator and a twin screw granulator with paracetamol formulations were examined by face-centered cubic design, which focused on investigating key performance metrics, namely, granule size, porosity, flowability and particle morphology of granules as a function of essential input process parameters (liquid content, throughput and rotation speed). Liquid and residence time distribution tests were also performed to gain insights into the liquid-powder mixing and flow behavior. The results indicated that continuous high shear granulation was more sensitive to process variation and produced spherical granules with monomodal size distribution and distinct internal structure and strength variation. Twin screw granulation with such a particular screw configuration showed narrower design space and granules were featured with multimodal size distribution, irregular shape, less detectible porosity difference and tighter range of strength. Granulation mechanisms explored on the basis of nucleation and growth regime maps revealed that for most cases liquid binder was uniformly distributed with fast droplet penetration into the powder bed and that granule consolidation and coalescence mainly took place in the nucleation, steady growth and rapid growth regimes.
authors.affiliation: Department of Pharmaceutics, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Lalith
authors.initials: L
authors.lastname: Kotamarthy
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Savitha
authors.initials: S
authors.lastname: Panikar
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46225, USA.
authors.forename: Maitraye
authors.initials: M
authors.lastname: Sen
authors.affiliation: School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Shankali
authors.initials: S
authors.lastname: Pradhan
authors.affiliation: Hüttlin GmbH - A Bosch Packaging Technology Company, 79650 Schopfheim, Germany.
authors.forename: Michaelis
authors.initials: M
authors.lastname: Marc
authors.affiliation: School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA; Department of Chemical and Biological Engineering, The University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: James D
authors.initials: JD
authors.lastname: Litster
authors.affiliation: Department of Pharmaceutics, Rutgers University, Piscataway, NJ 08854, USA; Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Muzzio
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: rohitrr@rci.rutgers.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Ramachandran
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D003627:Data Interpretation, Statistical; D007785:Lactose / Q000737:chemistry; D010316:Particle Size; D016062:Porosity; D012212:Rheology; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000706:statistics & numerical data*
chemical_list: D000082:Acetaminophen; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose
keywords: Continuous manufacturing; Design of experiments; Design space; Granulation mechanism; High shear granulation; Twin screw granulation