Non-invasive determination of ethanol, propylene glycol and water in a multi-component pharmaceutical oral liquid by direct measurement through amberplastic bottles using Fourier transform near-infrared spectroscopy

Fourier transform near-infrared (FT-NIR) spectroscopy was used to quantify rapidly the ethanol (34-49% v/v), propylene glycol (20-35% v/v) and water ( 11-20% m/m) contents within a multi-component pharmaceutical oral liquid by measurement directly through the amber plastic bottle packaging. Spectra w ere collected in the range 7302-12000 cm(-1) and calibration models set-up using partial least-squares regression (PLSR) and multiple linear regressio n. Reference values for the three components were measured using capillary gas chromatography (ethanol and propylene glycol) and Karl Fischer (water) assay procedures. The calibration and test sets consisted of production as well as laboratory batches that were made to extend the concentration range s beyond the natural production variation. The PLSR models developed gave s tandard errors of prediction (SEP) of 1.1% v/v for ethanol, 0.9% v/v for pr opylene glycol and 0.3% m/m for water. For each component the calibration m odel was validated in terms of: linearity, repeatability, intermediate prec ision and robustness. All the methods produced statistically favourable out comes. Ten production batches independent of the calibration and test sets were also challenged against the PLSR models, giving SEP values of 1.3% v/v (ethanol), 1.0% v/v (propylene glycol) and 0.2% m/m (water). NIR transmiss ion spectroscopy allowed all three liquid constituents to be non-invasively measured in under 1 min.