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Determination of Water Content in Ointments 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

Fatty ointments do not properly dissolve in methanol and thus require the addition of a solubiliser. Titration with specific KF solvents for oils and fats or / and the addition of decanol, chloroform or toluene is recommended. In addition, titration under warm conditions (50 °C) as well as use of a homogeniser are favourable. The coulometric method can only be applied after external extraction of the sample, however, it makes less sense in this specific case.

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
50 mL 188021 Aquastar™ - CombiSolvent fats - Solvent for volumetric Karl Fischer titration with one component reagents for fats
or
30 mL / 20 mL 188021 / 102445 Aquastar™ - CombiSolvent fats / Chloroform - solvent mixture for one component titration

Titration Parameters:
Extraction time: 180 sec. (60 sec. with homogeniser)
Temperaure: 40 - 50°C (if necessary)
Default titration settings, e.g.:
I(pol) = 20 - 50 µA, U(EP) = 100 - 250 mV
Stop criterion: drift < 20 µL/min

Sample size:
0.05 - 0.2 g

Procedure:
The titration medium is first placed into the titration cell and titrated dry by means of the titrant. Hereby the cell can be warmed up to 40 - 50 °C if necessary. Then the sample is added with a syringe without hollow needle (exact sample weight determination by weighing of syringe before and after injection) 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. (In the case of the use of an homogeniser the stirring time is reduced to 60 seconds.)

Titration two component system

Reagents:

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

Solvent
50 mL 188016 Aquastar™ - Solvent oils & fats - Solvent for volumetric Karl Fischer titration with two component reagents for oils & fats
or
30 mL / 20 mL 188016 / 102445 Aquastar™ - Solvent oils & fats / Chloroform - sovent mixture for two component titration

Titration Parameters:
Extraction time: 180 sec. ( 60 sec. with homogeniser)
Temperature: 40 - 50°C (if necessary)
Default titration settings, e.g.:
I(pol) = 20 - 50 µA, U(EP) = 100 - 250 mV
Stop criterion: drift < 20 µL/min

Sample size:
0.05 - 0.2 g

Procedure:
The titration medium is first placed into the titration cell and titrated dry by means of the titrant. Hereby the cell can be warmed up to 40 - 50 °C if necessary. Then the sample is added with a syringe without hollow needle (exact sample weight determination by weighing of syringe before and after injection) 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. (In the case of the use of an homogeniser the stirring time is reduced to 60 seconds.)

Materials

     
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