title: Implementation of transmission NIR as a PAT tool for monitoring drug transformation during HME processing.
abstract: The aim of the work reported herein was to implement process analytical technology (PAT) tools during hot melt extrusion (HME) in order to obtain a better understanding of the relationship between HME processing parameters and the extruded formulations. For the first time two in-line NIR probes (transmission and reflectance) have been coupled with HME to monitor the extrusion of the water insoluble drug indomethacin (IND) in the presence of Soluplus (SOL) or Kollidon VA64 hydrophilic polymers. In-line extrusion monitoring of sheets, produced via a specially designed die, was conducted at various drug/polymer ratios and processing parameters. Characterisation of the extruded transparent sheets was also undertaken by using DSC, XRPD and Raman mapping. Analysis of the experimental findings revealed the production of molecular solutions where IND is homogeneously blended (ascertained by Raman mapping) in the polymer matrices, as it acts as a plasticizer for both hydrophilic polymers. PCA analysis of the recorded NIR signals showed that the screw speed used in HME affects the recorded spectra but not the homogeneity of the embedded drug in the polymer sheets. The IND/VA64 and IND/SOL extruded sheets displayed rapid dissolution rates with 80% and 30% of the IND being released, respectively within the first 20min.
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Islam
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Scoutaris
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Maniruzzaman
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Hiren G
authors.initials: HG
authors.lastname: Moradiya
authors.affiliation: ThermoFisher Scientific, Stafford House, Boundary Way, Hemel Hempstead HP2 7GE, UK.
authors.forename: Sheelagh A
authors.initials: SA
authors.lastname: Halsey
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Michael S A
authors.initials: MS
authors.lastname: Bradley
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Babur Z
authors.initials: BZ
authors.lastname: Chowdhry
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Snowden
authors.affiliation: Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK. Electronic address: D.Douroumis@gre.ac.uk.
authors.forename: Dennis
authors.initials: D
authors.lastname: Douroumis
mesh_terms: D004867:Equipment Design; D006358:Hot Temperature; D057927:Hydrophobic and Hydrophilic Interactions; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry* / Q000592:standards; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D011786:Quality Control; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D011145:Polyvinyls; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D007213:Indomethacin
keywords: Hot-melt extrusion; In-line monitoring; Indomethacin; Molecular solutions; Near infrared spectroscopy; Process analytical technology; Raman mapping; Reflectance; Transmission