Metrohm near-infrared spectrometer in diffuse reflection mode is ideal for determining the residual moisture in a lyophilized pharmaceutical product.
Analysis of residual moisture in a lyophilised pharmaceutical product by near-infrared spectroscopy (NIRS)
Quantification of residual moisture in lyophilised parenteral products is an important measurement in the pharmaceutical industry. Analyses are routinely performed for process control and to insure that samples from production lots meet specified release parameters. For developmental purposes, such measurements are necessary during stability studies and optimisation of the freeze/pump cycles used in the freeze-drying process.
Traditional techniques for moisture determination
Traditional techniques for measuring moisture include Karl Fischer titration, gas chromatography, and thermo- gravimetric analysis, also known as loss-on-drying (LOD). Although these methods offer certain advantages with respect to sensitivity, solvent specificity, and system cost, they all suffer from the same drawbacks of being time consuming and destructive to the sample being analysed.
Near-infrared (NIR) spectroscopy ideal for moisture in freeze-dried materials
Near-infrared (NIR) spectroscopy has been shown to be an ideal method for rapidly measuring moisture in freeze-dried materials. Typical analysis times are less than 30 s. Calibrations for quantifying trace amounts of moisture are possible, due to the strong overtone absorption bands for water at 1940 nm and 1450 nm. In a diffuse reflectance configuration, the measurement may be performed through the bottom of the vial, since the borosilicate glass that is commonly used in ampoules and serum vials is «invisible» in the near-infrared region. Therefore, little or no sample preparation is required, and the need for costly or toxic reagents is eliminated. The technique is non-destructive and non-invasive; attributes that are particularly advantageous when analysing samples containing expensive active ingredients, or samples that may be used for stability studies since the same vials can be used for subsequent potency assays.
Diffuse reflection mode
Metrohm near-infrared spectrometer in diffuse reflection mode is ideal for determining the residual moisture in a lyophilized pharmaceutical product. Numerous sample vials containing freeze-dried pharmaceuticals were spiked with varying amounts of water for calibration purposes. The resulting differences in the absorption wavelengths of the OH-oscillation were correlated with the water content determined by Karl Fischer titration using the algorithm of multiple linear regression (MLR).
