title: Application of process analytical technology in tablet process development using NIR spectroscopy: blend uniformity, content uniformity and coating thickness measurements.
abstract: Near-infrared (NIR) spectroscopy was employed as a process analytical technique in three steps of tabletting process: to monitor the blend homogeneity, evaluate the content uniformity of tablets and determine the tablets coating thickness. A diode-array spectrometer mounted on a lab blender (SP15 NIR lab blender) was used to monitor blend uniformity using a calibration-free model with drug concentration ranging from 2.98 to 9.25% (w/w). The method developed accurately depicted the changes in concentration of the drug during blending and the positive effect of a delumping step in the production process. Blend homogeneity was reached within 2 min of the blending step post-delumping, with relative standard deviation (R.S.D.) values varying from 1.0 to 2.5% depending on the drug concentration of the blend. A Fourier-transform spectrometer (Bruker MPA) was used to analyze content uniformity and coating thickness with calibration based models. Prediction of a validation set with tablets compacted at pressures not present in the calibration set yielded an root mean square error of cross validation (RMSEP) of 1.94%; prediction of tablets compacted at pressures present in the calibration set yielded a RMSEP of 1.48%. Performance of the model was influenced by several physical tablet properties, which could be reduced by spectral pre-processing. A model based on reflectance spectra predicted coating thickness and its variation more accurately than the model based on transmission spectra. Inter-tablet coating variation was predicted with NIR and compared to reference thickness measurements. Both methods gave comparable results. Initial inter-tablet variation of tablets sampled in-process during coating was high, but stabilized after 30 min into the process.
authors.affiliation: Chemical and Pharmaceutical Development, Solvay Pharmaceuticals, van Houtenlaan 36, 1381 CP, Weesp, The Netherlands.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Moes
authors.forename: Marco M
authors.initials: MM
authors.lastname: Ruijken
authors.forename: Erik
authors.initials: E
authors.lastname: Gout
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.forename: Michael I
authors.initials: MI
authors.lastname: Ugwoke
mesh_terms: D002853:Chromatography, Liquid; D004339:Drug Compounding; D005079:Excipients; D015233:Models, Statistical; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D019265:Spectroscopy, Near-Infrared; D013608:Tablets, Enteric-Coated / Q000032:analysis / Q000592:standards*
chemical_list: D005079:Excipients; D013608:Tablets, Enteric-Coated