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

摘要

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% rn/rn) contents within a multi-component pharmaceutical oral liquid by measurement directly through the amber plastic bottle packaging. Spectra were collected in the range 7302—12 000 cm~1 and calibration models set-up using partial least-squares regression (PLSR) and multiple linear regression. 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 ranges beyond the natural production variation. The PLSR models developed gave standard errors of prediction (SEP) of 1.1% v/v for ethanol, 0.9% v/v for propylene glycol and 0.3% in/rn for water. For each component the calibration model was validated in terms of: linearity, repeatability, intermediate precision and robustness. All the methods produced statistically favourable outcomes. 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% rn/rn (water). NIR transmission spectroscopy allowed all three liquid constituents to be non-invasively measured in under 1 mm.