Mixing and transport during pharmaceutical twin-screw wet granulation: experimental analysis via chemical imaging.
Twin-screw granulation is a promising continuous alternative for traditional batch high shear wet granulation (HSWG). The extent of HSWG in a twin screw granulator (TSG) is greatly governed by the residence time of the granulation materials in the TSG and degree of mixing. In order to determine the residence time distribution (RTD) and mixing in TSG, mostly visual observation and particle tracking methods are used, which are either inaccurate and difficult for short RTD, or provide an RTD only for a finite number of preferential tracer paths. In this study, near infrared chemical imaging, which is more accurate and provides a complete RTD, was used. The impact of changes in material throughput (10-17 kg/h), screw speed (500-900 rpm), number of kneading discs (2-12) and stagger angle (30-90°) on the RTD and axial mixing of the material was characterised. The experimental RTD curves were used to calculate the mean residence time, mean centred variance and the Péclet number to determine the axial mixing and predominance of convective over dispersive transport. The results showed that screw speed is the most influential parameter in terms of RTD and axial mixing in the TSG and established a significant interaction between screw design parameters (number and stagger angle of kneading discs) and the process parameters (material throughput and number of kneading discs). The results of the study will allow the development and validation of a transport model capable of predicting the RTD and macro-mixing in the TSG. These can later be coupled with a population balance model in order to predict granulation yields in a TSG more accurately.
BIOMATH, Dept. of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Gent, Belgium; Laboratory of Pharmaceutical Process Analytical Technology, Dept. of Pharmaceutical Analysis, Ghent University, Ghent, Belgium. Electronic address: ashish.kumar@ugent.be.
Ashish
A
Kumar
Laboratory of Pharmaceutical Technology, Dept. of Pharmaceutics, Ghent University, Ghent, Belgium. Electronic address: jurgen.vercruysse@ugent.be.
Jurgen
J
Vercruysse
VTT Technical Research Centre of Finland, Optical Measurement Technologies, Kuopio, Finland. Electronic address: maunu.toiviainen@vtt.fi.
Maunu
M
Toiviainen
VTT Technical Research Centre of Finland, Optical Measurement Technologies, Kuopio, Finland. Electronic address: pierre-emmanuel.panouillot@vtt.fi.
Pierre-Emmanuel
PE
Panouillot
VTT Technical Research Centre of Finland, Optical Measurement Technologies, Kuopio, Finland. Electronic address: mikko.juuti@vtt.fi.
Mikko
M
Juuti
Laboratory of Pharmaceutical Technology, Dept. of Pharmaceutics, Ghent University, Ghent, Belgium. Electronic address: valerie.vanhoorne@ugent.be.
Valérie
V
Vanhoorne
Laboratory of Pharmaceutical Technology, Dept. of Pharmaceutics, Ghent University, Ghent, Belgium. Electronic address: chris.vervaet@ugent.be.
Chris
C
Vervaet
Laboratory of Pharmaceutical Technology, Dept. of Pharmaceutics, Ghent University, Ghent, Belgium. Electronic address: jeanpaul.remon@UGent.be.
Jean Paul
JP
Remon
CAPEC-PROCESS, Chemical and Biochemical Engineering, Technical University of Denmark, Kongens Lyngby, Denmark. Electronic address: kvg@kt.dtu.dk.
Krist V
KV
Gernaey
Laboratory of Pharmaceutical Process Analytical Technology, Dept. of Pharmaceutical Analysis, Ghent University, Ghent, Belgium. Electronic address: thomas.debeer@ugent.be.
Thomas
T
De Beer
BIOMATH, Dept. of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Gent, Belgium. Electronic address: ingmar.nopens@ugent.be.
Ingmar
I
Nopens
D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D005079:Excipients / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D012212:Rheology; D019265:Spectroscopy, Near-Infrared; D013678:Technology, Pharmaceutical / Q000379:methods*; D013806:Theophylline / Q000737:chemistry*; D013997:Time Factors
D004304:Dosage Forms; D005079:Excipients; D013806:Theophylline; D007785:Lactose
Axial mixing; Flow regime; NIR chemical imaging; Residence time distribution; Screw configuration; Twin-screw granulation