Product category:
Titration equipment
News Release from: Metrohm UK | Subject: KF oven technique
Edited by the Laboratorytalk Editorial
Team on 31 March 2008
Water in pharmaceuticals by automated
Karl Fischer
The Karl Fischer (KF) oven method permits determination of the water content of pharmaceuticals that are not amenable to direct KF titration because they either undergo detrimental side reactions
Water determinations carried out with several pharmaceuticals demonstrate that the values obtained with the KF Oven Method all lie within the ranges specified in the European Pharmacopoeia Moreover, the automated KF oven technique significantly enhances sample throughput and repeatability of the results
This article was originally published on Laboratorytalk on 23 Jan 2003 at 8.00am (UK)
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Quality and shelf life of active pharmaceutical ingredients depend primarily on the content of adsorbed (surface water) or bound water (water of crystallisation).
Although the 4th Edition of the European Pharmacopeia (2002) describes the direct Karl Fischer (KF) titration as the most important method for determining the water content, in some cases, where substances undergo side reactions with the KF reagents or where they release their water only at high temperatures, the European Pharmacopeia recommends the quantification via the loss on drying (LOD) in a drying cabinet or desiccator.
However, besides the water to be determined, this method also includes all volatile compounds (e.g impurities, degradation products) released at higher temperatures.
Further reading
Basic theory of Karl Fischer titration
The determination of moisture content of a sample by coulometric and volumetric means using Metrohm equipment explained in detail
Moisture analysis in the pharmaceutical industry
Moisture analysis is a critical parameter during the manufacture of solid pharmaceutical bulk drugs. New equipment from Metrohm promises to make life easier
The KF oven method allows to resolve the above-mentioned problems.
Depending on the water content of the sample, the KF titration can be performed either volumetrically for higher or coulometrically for lower water contents.
Considering the relatively small amount of water in most pharmaceuticals, samples were analysed coulometrically.
The calculation of the sample's water content involves also the determination of the humidity in the sample vessel and the moisture adhering to the vessel surface, vial cap and septum.
Three empty but sealed sample vials are analysed under the same conditions as the particular sample.
The resulting mean value is stored as a blank value and automatically taken into account in the calculation.
Subsequently a threefold determination for each compound is performed.
Accuracy of the KF titrations is checked at regular intervals with a certified KF oven standard.
The optimum oven temperature for driving off the water should ensure complete water extraction in a reasonable time excluding decomposition of the sample.
This means that the oven temperature should be chosen as high as possible to ensure short determination times, but still be 20 to 30C below the decomposition temperature.
The oven temperatures for unknown samples are determined on the basis of the water-release curves that were recorded for all investigated pharmaceuticals in the temperature range 50 to 250C. Request a free brochure from Metrohm UK ...
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