title: Towards a real time release approach for manufacturing tablets using NIR spectroscopy.
abstract: The aim of this study was to use the near-infrared spectroscopy (NIRS) as a process analytical tool to evaluate the conformity of paracetamol tablets in terms of four Pharmacopoeia tests (content uniformity, hardness, disintegration time, friability) and to control in-line blend uniformity. Tablets were manufactured by direct compression. Three different active pharmaceutical ingredient (API) concentrations were manufactured and three different compaction pressures were used. Intact tablets were analysed by transmission mode with NIRS prior to European Pharmacopoeia tests that were used as reference methods. Partial least square (PLS) regression was selected to build the prediction NIR models for content uniformity, tablet hardness and disintegration time. The prediction of NIR content uniformity and tablet hardness methods were validated using the accuracy profile approach. The values of the root mean squared error of calibration (RMSEC) and the root mean squared error of prediction (RMSEP) for the disintegration time indicated the robustness and the global accuracy of the NIR model. Regarding the tablet friability test, the classification was based on K-nearest neighbours (KNN). Then tablet NIR analyses successfully allowed the prediction of their conformity. Compared to the time consuming Pharmacopoeia reference methods, the benefit of this nondestructive method is significant, especially for reducing batch release time.
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium. Electronic address: Aude.Pestieau@ulg.ac.be.
authors.forename: Aude
authors.initials: A
authors.lastname: Pestieau
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Krier
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium.
authors.forename: Grégory
authors.initials: G
authors.lastname: Thoorens
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Dupont
authors.affiliation: Laboratory of Analytical Chemistry, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Chavez
authors.affiliation: Laboratory of Analytical Chemistry, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Ziemons
authors.affiliation: Laboratory of Analytical Chemistry, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hubert
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Evrard
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D006244:Hardness; D016018:Least-Squares Analysis; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013607:Tablets / Q000737:chemistry*
chemical_list: D013607:Tablets
keywords: Blend uniformity; Near-infrared spectroscopy; Process analytical technology; Real time release; Tablet testing