title: A novel in-line NIR spectroscopy application for the monitoring of tablet film coating in an industrial scale process.
abstract: Film coating of tablets is a multivariate pharmaceutical unit operation. In this study an innovative in-line Fourier-Transform Near-Infrared Spectroscopy (FT-NIRS) application is described which enables real-time monitoring of a full industrial scale pan coating process of heart-shaped tablets. The tablets were coated with a thin hydroxypropyl methylcellulose (HPMC) film of up to approx. 28 μm on the tablet face as determined by SEM, corresponding to a weight gain of 2.26%. For a better understanding of the aqueous coating process the NIR probe was positioned inside the rotating tablet bed. Five full scale experimental runs have been performed to evaluate the impact of process variables such as pan rotation, exhaust air temperature, spray rate and pan load and elaborate robust and selective quantitative calibration models for the real-time determination of both coating growth and tablet moisture content. Principal Component (PC) score plots allowed each coating step, namely preheating, spraying and drying to be distinguished and the dominating factors and their spectral effects to be identified (e.g. temperature, moisture, coating growth, change of tablet bed density, and core/coat interactions). The distinct separation of HPMC coating growth and tablet moisture in different PCs enabled a real-time in-line monitoring of both attributes. A PLS calibration model based on Karl Fischer reference values allowed the tablet moisture trajectory to be determined throughout the entire coating process. A 1-latent variable iPLS weight gain calibration model with calibration samples from process stages dominated by the coating growth (i.e. ≥ 30% of the theoretically applied amount of coating) was sufficiently selective and accurate to predict the progress of the thin HPMC coating layer. At-line NIR Chemical Imaging (NIR-CI) in combination with PLS Discriminant Analysis (PLSDA) verified the HPMC coating growth and physical changes at the core/coat interface during the initial stages of the coating process. In addition, inter- and intra-tablet coating variability throughout the process could be assessed. These results clearly demonstrate that in-line NIRS and at-line NIR-CI can be applied as complimentary PAT tools to monitor a challenging pan coating process.
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Department of Pharmaceutical Technology and Biopharmaceutics, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: C-V
authors.initials: CV
authors.lastname: Möltgen
authors.forename: T
authors.initials: T
authors.lastname: Puchert
authors.forename: J C
authors.initials: JC
authors.lastname: Menezes
authors.forename: D
authors.initials: D
authors.lastname: Lochmann
authors.forename: G
authors.initials: G
authors.lastname: Reich
mesh_terms: D002138:Calibration; D004339:Drug Compounding / Q000592:standards; D005079:Excipients / Q000737:chemistry; D006813:Humidity; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D025341:Principal Component Analysis; D012107:Research Design; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets / Q000737:chemistry* / Q000592:standards; D014894:Weights and Measures
chemical_list: D005079:Excipients; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose