Application of process analytical technology in tablet process development using NIR spectroscopy: blend uniformity, content uniformity and coating thickness measurements.

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.