Net analyte signal based statistical quality control.

Net analyte signal statistical quality control (NAS-SQC) is a new methodology to perform multivariate product quality monitoring based on the net analyte signal approach. The main advantage of NAS-SQC is that the systematic variation in the product due to the analyte (or property) of interest is separated from the remaining systematic variation due to all other compounds in the matrix. This enhances the ability to flag products out of statistical control. Using control charts, the analyte content, variation of other compounds, and residual variation can be monitored. As an example, NAS-SQC is used to appreciate the control content uniformity of a commercially available pharmaceutical tablet product measured with near-infrared spectroscopy. Using the NAS chart, the active pharmaceutical ingredient (API) content is easily monitored for new tablets. However, since quality is a multivariate property, other quality parameters of the tablets are also monitored simultaneously. It will be demonstrated that, besides the API content, the water content of the tablets as well as the homogeneity of the other compounds is monitored.

Application of transmission near-infrared spectroscopy to uniformity of content testing of intact steroid tablets.

Transmission near-infrared (NIR) spectroscopy was used for the rapid and non-destructive determination of the content of a hormone steroid in single intact tablets. Tablets produced for clinical trial purposes containing 5, 10, 15, 20 and 30 mg (2.94, 5.88, 8.82, 11.76 and 17.64% m/m, respectively) were used to develop calibration models without the need to specially prepare any out of specification tablets. Reference values for the individual tablets used in the NIR calibration models and test set were measured by reversed-phase high performance liquid chromatography (HPLC). Partial least squares regression using standard normal variate transformed second-derivative spectra over the range 800 to 1040 nm gave the optimum calibration model with a standard error of calibration of 0.52 mg per tablet. Measurements of an independent test set gave comparable results (standard error of prediction 0.31 mg per tablet). Measurement errors for a single tablet (RSD < 2.5% for a given active level) were sufficiently small to allow the procedure to be applied to pharmacopoeial uniformity of content testing of batches of these tablets and permitted the non-destructive testing of 30 tablets in under 20 min as compared to 6 h by HPLC.

Non-invasive determination of ethanol, propylene glycol and water in a multi-component pharmaceutical oral liquid by direct measurement through amber plastic 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 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% m/m 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% m/m (water). NIR transmission spectroscopy allowed all three liquid constituents to be non-invasively measured in under 1 min.