title: Near infra red spectroscopy as a multivariate process analytical tool for predicting pharmaceutical co-crystal concentration.
abstract: The use of near infra red spectroscopy to predict the concentration of two pharmaceutical co-crystals; 1:1 ibuprofen-nicotinamide (IBU-NIC) and 1:1 carbamazepine-nicotinamide (CBZ-NIC) has been evaluated. A partial least squares (PLS) regression model was developed for both co-crystal pairs using sets of standard samples to create calibration and validation data sets with which to build and validate the models. Parameters such as the root mean square error of calibration (RMSEC), root mean square error of prediction (RMSEP) and correlation coefficient were used to assess the accuracy and linearity of the models. Accurate PLS regression models were created for both co-crystal pairs which can be used to predict the co-crystal concentration in a powder mixture of the co-crystal and the active pharmaceutical ingredient (API). The IBU-NIC model had smaller errors than the CBZ-NIC model, possibly due to the complex CBZ-NIC spectra which could reflect the different arrangement of hydrogen bonding associated with the co-crystal compared to the IBU-NIC co-crystal. These results suggest that NIR spectroscopy can be used as a PAT tool during a variety of pharmaceutical co-crystal manufacturing methods and the presented data will facilitate future offline and in-line NIR studies involving pharmaceutical co-crystals.
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK. Electronic address: clivewood@outlook.com.
authors.forename: Clive
authors.initials: C
authors.lastname: Wood
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK.
authors.forename: Abdolati
authors.initials: A
authors.lastname: Alwati
authors.affiliation: Thermo Fisher Scientific, Stafford House, Boundary Way, Hemel Hempstead, HP2 7GE, UK.
authors.forename: Sheelagh
authors.initials: S
authors.lastname: Halsey
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Gough
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Brown
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Kelly
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, UK.
authors.forename: Anant
authors.initials: A
authors.lastname: Paradkar
mesh_terms: D002138:Calibration; D002220:Carbamazepine / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D007052:Ibuprofen / Q000737:chemistry; D016018:Least-Squares Analysis; D015999:Multivariate Analysis; D009536:Niacinamide / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders; D009536:Niacinamide; D002220:Carbamazepine; D007052:Ibuprofen
keywords: Active pharmaceutical ingredient; Co-crystal; NIR spectroscopy; Partial least squares; Prediction; Process analytical tool