title: The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation.
abstract: Twin screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to continuous granulation of moisture sensitive drugs. However, knowledge of the material behavior during TS HMG is crucial to optimize the formulation, process and resulting granule properties. The aim of this study was to evaluate the agglomeration mechanism during TS HMG using a rheometer in combination with differential scanning calorimetry (DSC).
  
  
  
  An immiscible drug-binder formulation (caffeine-Soluplus(®)) was granulated via TS HMG in combination with thermal and rheological analysis (conventional and Rheoscope), granule characterization and Near Infrared chemical imaging (NIR-CI).
  
  
  
  A thin binder layer with restricted mobility was formed on the surface of the drug particles during granulation and is covered by a second layer with improved mobility when the Soluplus(®) concentration exceeded 15% (w/w). The formation of this second layer was facilitated at elevated granulation temperatures and resulted in smaller and more spherical granules.
  
  
  
  The combination of thermal and rheological analysis and NIR-CI images was advantageous to develop in-depth understanding of the agglomeration mechanism during continuous TS HMG and provided insight in the granule properties as function of process temperature and binder concentration.
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. Tinne.Monteyne@Ugent.be.
authors.forename: Tinne
authors.initials: T
authors.lastname: Monteyne
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
authors.forename: Liza
authors.initials: L
authors.lastname: Heeze
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.|BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653,, 9000, Ghent, Belgium.
authors.forename: Severine Therese F C
authors.initials: ST
authors.lastname: Mortier
authors.affiliation: Center for Material Characterization of Products, Thermo sher Dieselstrasse 4,, 76227, Karlsruhe, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Oldörp
authors.affiliation: Polymer Technology, Department of Mechanical Engineering, Eindhoven University of Technology, Gemini-Zuid 4.142, 5600, Eindhoven, The Netherlands.
authors.forename: Ruth
authors.initials: R
authors.lastname: Cardinaels
authors.affiliation: BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653,, 9000, Ghent, Belgium.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Nopens
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460,, 9000, Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460,, 9000, Ghent, Belgium.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000138:chemical synthesis; D012212:Rheology / Q000379:methods*; D013696:Temperature
chemical_list: D004364:Pharmaceutical Preparations
keywords: agglomeration mechanism; caffeine anhydrous; glass transition temperature; granule properties; soluplus®; tan(δ)