title: Active content determination of pharmaceutical tablets using near infrared spectroscopy as Process Analytical Technology tool.
abstract: The aim of this study was to develop Near infrared (NIR) methods to determine the active content of non-coated pharmaceutical tablets manufactured from a proportional tablet formulation. These NIR methods intend to be used for the monitoring of the active content of tablets during the tableting process. Firstly, methods were developed in transmission and reflection modes to quantify the API content of the lowest dosage strength. Secondly, these methods were fully validated for a concentration range of 70-130% of the target active content using the accuracy profile approach based on β-expectation tolerance intervals. The model using the transmission mode showed a better ability to predict the right active content compared to the reflection one. However, the ability of the reflection mode to quantify the API content in the highest dosage strength was assessed. Furthermore, the NIR method based on the transmission mode was successfully used to monitor at-line the tablet active content during the tableting process, providing better insight of the API content during the process. This improvement of control of the product quality provided by this PAT method is thoroughly compliant with the Quality by Design (QbD) concept. Finally, the transfer of the transmission model from the off-line to an on-line spectrometer was efficiently investigated.
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium. Electronic address: pfchavez@ulg.ac.be.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Chavez
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Sacré
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: De Bleye
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Lauranne
authors.initials: L
authors.lastname: Netchacovitch
authors.affiliation: UCB Pharma S.A., Avenue de l'Industrie, 1420 Braine-l'Alleud, Belgium.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mantanus
authors.affiliation: UCB Pharma S.A., Avenue de l'Industrie, 1420 Braine-l'Alleud, Belgium.
authors.forename: Henri
authors.initials: H
authors.lastname: Motte
authors.affiliation: UCB Pharma S.A., Avenue de l'Industrie, 1420 Braine-l'Alleud, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Schubert
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hubert
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Ziemons
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013607:Tablets
chemical_list: D004364:Pharmaceutical Preparations; D013607:Tablets
keywords: Active content; Near infrared spectroscopy; Pharmaceutical tablets; Process Analytical Technology; Quality by Design; Validation