title: A novel transflectance near infrared spectroscopy technique for monitoring hot melt extrusion.
abstract: A transflectance near infra red (NIR) spectroscopy approach has been used to simultaneously measure drug and plasticiser content of polymer melts with varying opacity during hot melt extrusion. A high temperature reflectance NIR probe was mounted in the extruder die directly opposed to a highly reflective surface. Carbamazepine (CBZ) was used as a model drug, with polyvinyl pyrollidone-vinyl acetate co-polymer (PVP-VA) as a matrix and polyethylene glycol (PEG) as a plasticiser. The opacity of the molten extrudate varied from transparent at low CBZ loading to opaque at high CBZ loading. Particulate amorphous API and voids formed around these particles were found to cause the opacity. The extrusion process was monitored in real time using transflectance NIR; calibration and validation runs were performed using a wide range of drug and plasticiser loadings. Once calibrated, the technique was used to simultaneously track drug and plasticiser content during applied step changes in feedstock material. Rheological and thermal characterisations were used to help understand the morphology of extruded material. The study has shown that it is possible to use a single NIR spectroscopy technique to monitor opaque and transparent melts during HME, and to simultaneously monitor two distinct components within a formulation.
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK. Electronic address: A.L.Kelly@Bradford.ac.uk.
authors.forename: A L
authors.initials: AL
authors.lastname: Kelly
authors.affiliation: Thermo Fisher Scientific, Stafford House, Boundary Way, Hemel Hempstead HP2 7GE, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Halsey
authors.affiliation: Thermo Fisher Scientific, Stafford House, Boundary Way, Hemel Hempstead HP2 7GE, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Bottom
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK.
authors.forename: S
authors.initials: S
authors.lastname: Korde
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK.
authors.forename: T
authors.initials: T
authors.lastname: Gough
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK.
authors.forename: A
authors.initials: A
authors.lastname: Paradkar
mesh_terms: D002138:Calibration; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D006358:Hot Temperature; D010968:Plasticizers / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D012212:Rheology; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D010968:Plasticizers; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D002220:Carbamazepine; D011092:Polyethylene Glycols
keywords: Carbamazepine; Hot melt extrusion; Near infrared spectroscopy; PVP-VA; Process analytical technology