Tinne Monteyne1, Liza Heeze2, Severine Therese F C Mortier2,3, Klaus Oldörp4, Ruth Cardinaels5, Ingmar Nopens3, Chris Vervaet6, Jean-Paul Remon6, Thomas De Beer2. 1. 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. 2. Laboratory of Pharmaceutical Process Analytical Technology Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. 3. BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653,, 9000, Ghent, Belgium. 4. Center for Material Characterization of Products, Thermo sher Dieselstrasse 4,, 76227, Karlsruhe, Germany. 5. Polymer Technology, Department of Mechanical Engineering, Eindhoven University of Technology, Gemini-Zuid 4.142, 5600, Eindhoven, The Netherlands. 6. Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460,, 9000, Ghent, Belgium.
Abstract
PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSION: 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: Jurgen Vercruysse; Maunu Toiviainen; Margot Fonteyne; Niko Helkimo; Jarkko Ketolainen; Mikko Juuti; Urbain Delaet; Ivo Van Assche; Jean Paul Remon; Chris Vervaet; Thomas De Beer Journal: Eur J Pharm Biopharm Date: 2013-11-06 Impact factor: 5.571
Authors: J Vercruysse; D Córdoba Díaz; E Peeters; M Fonteyne; U Delaet; I Van Assche; T De Beer; J P Remon; C Vervaet Journal: Eur J Pharm Biopharm Date: 2012-06-09 Impact factor: 5.571
Authors: Jay P Lakshman; James Kowalski; Madhav Vasanthavada; Wei-Qin Tong; Yatindra M Joshi; Abu T M Serajuddin Journal: J Pharm Sci Date: 2010-12-03 Impact factor: 3.534