title: Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging.
abstract: Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw granulation is not yet fully understood. Therefore, this study aims at visualizing the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw granulation system.
authors.affiliation: Department of Pharmaceutics, Ghent University, Belgium.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Vercruysse
authors.affiliation: Optical Measurement Technologies, VTT Technical Research Centre, Kuopio, Finland.
authors.forename: Maunu
authors.initials: M
authors.lastname: Toiviainen
authors.affiliation: Department of Pharmaceutical Analysis, Ghent University, Belgium.
authors.forename: Margot
authors.initials: M
authors.lastname: Fonteyne
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Niko
authors.initials: N
authors.lastname: Helkimo
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Ketolainen
authors.affiliation: Optical Measurement Technologies, VTT Technical Research Centre, Kuopio, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Juuti
authors.affiliation: Department of Pharmaceutical Development, Johnson&Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Belgium.
authors.forename: Urbain
authors.initials: U
authors.lastname: Delaet
authors.affiliation: Department of Pharmaceutical Development, Johnson&Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Belgium.
authors.forename: Ivo
authors.initials: I
authors.lastname: Van Assche
authors.affiliation: Department of Pharmaceutics, Ghent University, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Department of Pharmaceutics, Ghent University, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Department of Pharmaceutical Analysis, Ghent University, Belgium. Electronic address: Thomas.DeBeer@UGent.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D032882:Comprehension; D059627:Liquid Phase Microextraction / Q000295:instrumentation / Q000379:methods*; D010316:Particle Size; D011208:Powders; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000379:methods*
chemical_list: D011208:Powders
keywords: Granulation liquid distribution; NIR chemical imaging; Process understanding; Twin screw granulation