Determination of Water Content in Tablet Using Karl Fischer Titration

Product Group

Pharmaceuticals

General Information Concerning the Product Group

Pharmaceuticals

Pharmaceutical products are often characterized by complex formulations. Difficulties observed during Karl Fischer determination are often caused by the limited solubility. In some cases side reactions have to be considered. In dependance of composition and properties of the formulations, various measures are necessary for an undisturbed Karl Fischer determination. In pharmaceutical guidelines (USP, Ph Eur, DAB) the Karl Fischer titration is described as common method for water determination. For some substances special procedures can be found. The determination of mass loss as method for water determination is not recommended.

Special Information Concerning the Sample and the Methods

Paracetamol tablets are not completely soluble in common Karl Fischer reagents, but the results are reproducible. Addition of formamide as solubiliser leads to a slightly better solubility. The indirect coulometric titration in combination with the Karl Fischer oven technique at 170 °C shows reproducible results and is therfore recommended.

Titration One Component System

Reagents:

Titrant
188005 Aquastar^® - CombiTitrant 5 - One component reagent for volumetric Karl Fischer titration, 1 mL = approx. 5 mg water

Solvent
40 mL 188008 Aquastar^® - CombiSolvent - Methanol-free solvent for volumetric Karl Fischer titration with one component reagents
and
20 mL 109684 Formamide - as solubiliser

Titration Parameters:
Stirring time: 300 sec.
Default titration settings, e.g.:
I(pol) = 20 - 50 µA, U(EP) = 100 - 250 mV
Stop criterion: drift < 20 µL/min

Sample size:
50 mg

Procedure:
The titration medium is first placed into the titration cell and titrated dry by means of the titrant. Then the sample is added from a weighing boat (exact sample weight determination by weighing of weighing boat before and after addition) and the titration is started. For complete extraction of the sample a stirring time of at least 300 seconds is recommended. Analysis of approximately 150 mg sample is possible, before the Karl Fischer solvent needs to be changed.