Determination of Water Content in Tablets 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

A precondition of water determination is the painstaking crushing of the tablets. At least four capsules are powdered in a mortar (please mind hygroscopic properties!) In the case of solubility problems various solubilisers can be added to the KF solvent: e.g. formamide for saline compounds or long-chain alcohols for compounds with low polarity. In addition, titration under warm conditions (50 °C) as well as the use of a homogeniser are favourable (accelerated dissolution of the sample or rather extraction of the water). Through utilisation of a titrant with a factor of less than 5 mg/mL the sample size can be reduced. With stable end points it is possible to also titrate within suspension, however, only the extracted water is determined. An alternative to the direct volumetric titration are both, the external extraction as well as the KF oven technique: during external extraction the sample is dissolved, or rather extracted in a suitable solvent. An aliquote is then analysed volumetrically or coulometrically. The result must be corrected for the blank value of the solvent. With the KF oven technique the water is released by heating the sample to an appropriate temperature and transferred into a volumetric or coulometric cell.

Titration one component system

Reagents:

Titrant
188005 Aquastar™ - CombiTitrant 5 - One component reagent for volumetric Karl Fischer titration, 1 mL = approx. 5 mg water
or
188002 Aquastar™ - CombiTitrant 2 - One component reagent for volumetric Karl Fischer titration, 1 mL = approx. 2 mg water

Solvent
50 mL 188009 Aquastar™ - CombiMethanol - Solvent for volumetric Karl Fischer titration with one component reagents, max. 0.01 % water
or
30 mL / 20 mL 188009 / 109684 CombiMethanol / Formamide - or other solvents with at least 50 % methanol, e.g. CombiMethanol / Decanol

Titration Parameters:
Extraction time: 180 sec.
(Temperature 50 °C)
Default titration settings, e.g.:
I(pol) = 20 - 50 µA, U(EP) = 100 - 250 mV
Stop criterion: drift < 20 µL/min

Sample size:
0.2 - 0.5 g (powdered)

Procedure:
The titration medium is first placed into the 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 dissolution of the sample or rather full extraction of the water a stirring time of 180 seconds is recommended. For hardly soluble substances the titration cell is heated to 50 °C.

Titration two component system

Reagents:

Titrant
188010 Aquastar™ - Titrant 5 - Titrant for volumetric titration with two component reagents, 1 mL = approx. 5 mg water
or
188011 Aquastar™ - Titrant 2 - Titrant for volumetric titration with two component reagents, 1 mL = approx. 2 mg water

Solvent
50 mL 188015 Aquastar™ - Solvent - Solvent for volumetric titration with two component reagents
or
30 mL / 20 mL 188015 / 109684 Aquastar™ - Solvent / Formamide - or other solvents with at least 50 % Aquastar™ - Solvent, e.g. Aquastar™ - Solvent / Decanol

Titration Parameters:
Extraction time: 180 sec.
(Temperature 50 °C)
Default titration settings, e.g.:
I(pol) = 20 - 50 µA, U(EP) = 100 - 250 mV
Stop criterion: drift < 20 µL/min

Sample size:
0.2 - 0.5 g (powdered)

Procedure:
The titration medium is first placed into the 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 dissolution of the sample or rather full extraction of the water a stirring time of 180 seconds is recommended. For hardly soluble substances the titration cell is heated to 50 °C.

Materials

     
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