title: In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion.
abstract: The aim was to evaluate near-infrared spectroscopy for the in-line determination of the drug concentration, the polymer-drug solid-state behaviour and molecular interactions during hot-melt extrusion. Kollidon® SR was extruded with varying metoprolol tartrate (MPT) concentrations (20%, 30% and 40%) and monitored using NIR spectroscopy. A PLS model allowed drug concentration determination. The correlation between predicted and real MPT concentrations was good (R(2)=0.97). The predictive performance of the model was evaluated by the root mean square error of prediction, which was 1.54%. Kollidon® SR with 40% MPT was extruded at 105°C and 135°C to evaluate NIR spectroscopy for in-line polymer-drug solid-state characterisation. NIR spectra indicated the presence of amorphous MPT and hydrogen bonds between drug and polymer in the extrudates. More amorphous MPT and interactions could be found in the extrudates produced at 135°C than at 105°C. Raman spectroscopy, DSC and ATR FT-IR were used to confirm the NIR observations. Due to the instability of the formulation, only in-line Raman spectroscopy was an adequate confirmation tool. NIR spectroscopy is a potential PAT-tool for the in-line determination of API concentration and for the polymer-drug solid-state behaviour monitoring during pharmaceutical hot-melt extrusion.
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Harelbekestraat 72, Ghent, Belgium. Lien.Saerens@UGent.be
authors.forename: Lien
authors.initials: L
authors.lastname: Saerens
authors.forename: Lien
authors.initials: L
authors.lastname: Dierickx
authors.forename: Thomas
authors.initials: T
authors.lastname: Quinten
authors.forename: Peter
authors.initials: P
authors.lastname: Adriaensens
authors.forename: Robert
authors.initials: R
authors.lastname: Carleer
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D004355:Drug Stability; D006358:Hot Temperature; D006860:Hydrogen Bonding; D016018:Least-Squares Analysis; D008790:Metoprolol / Q000737:chemistry*; D015233:Models, Statistical; D011108:Polymers / Q000737:chemistry; D011205:Povidone / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013059:Spectrum Analysis, Raman
chemical_list: D011108:Polymers; D011205:Povidone; D008790:Metoprolol