Moisture Content Analysis
BTL is able to offer a moisture content analysis service for freeze dried products, using the Karl Fischer Coulometric Titration method.
Why is Residual Moisture Determination Necessary?
This is necessary:-
- In freeze-drying research and development, in order to optimise freeze-drying cycles
- For regulatory purposes, in order to standardise batch-to-batch processing of freeze-dried pharmaceuticals or reagents
- During validation for both the above, and to avoid areas of extremes or high or low residual moisture values which can be damaging to the product.
Karl Fischer Titration
Karl Fischer Titration is a sensitive method for determining the amount of moisture in small masses of material precisely and accurately. It is based on the Bunsen Reaction that takes place between iodine and sulphur dioxide in aqueous mediums. There are two types of methods: Volumetric, which is used for ppm levels up to 100%, and Coulometric, which is used for moisture levels between 10 micrograms to 10mgs of water in a sample.
Coulometric Karl Fischer Titration
One problem with conventional Karl Fischer titrations is that it is necessary to dry all solvents used to extract moisture from the lyophilised powder. The Coulometric titrator is able to self-purge, constantly drying reagent within the vessel. Dry reagent can be removed from the reaction vessel, injected into the vial and then added back to the reaction vessel. Reagent can therefore be used for a considerable time, since the reagent is regenerated.
With coulometric titration, the iodine necessary for the reaction is produced in situ, by electrolysis of iodide to free iodine. The system releases only sufficient I2 to react with the water in the sample. The amount of moisture present is determined by measuring the amount of current generated during the titration.
At Biopharma Technology, GR Scientific "Cou-Lo" Compact Karl Fischer is used for routine estimation of freeze-dried sample moisture contents.
13th March 2005