Determination of Water Content in Suppositories 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

Suppositories are slow to dissolve in methanolic media. For an increase in the rate of dissolution a solubiliser (e.g. toluene or long-chain alcohols) can be added. In addition, titration under warm conditions (50 °C) as well as use of a homogeniser are favourable. Through utilisation of a titrant with a factor of less than 5 mg/mL the sample size can be reduced. The sample is chipped with a knife. Coulometric analysis is only possible after external extraction of the sample. Hereby the sample is dissolved, or rather extracted, in an appropriate solvent.

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

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 - 1.0 g

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

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 - 1.0 g

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.

Coulometry with diaphragm

Reagents:

Catholyte
5 mL 109255 Aquastar™ - CombiCoulomat frit - Coulometric Karl Fischer reagent for cells with diaphragm

Anolyte
100 mL 109255 Aquastar™ - CombiCoulomat frit - Coulometric Karl Fischer reagent for cells with diaphragm

Titration Parameters:
Default coulometer settings for cell with diaphragm:
For end point indication, e.g.:
I(pol) = 5 - 10 µA, U(EP) = 50 - 100 mV
Stop criterion: drift < 20 µg/min

Sample size:
Solution of 1 g in 50 mL methanol or appropriate solvent mixture

Procedure:
The Karl-Fischer reagent is placed into the cathode and anode compartment of the titration cell with diaphragm. The coulometer is started and the solvent is titrated dry. After preliminary titration and stabilisation of drift an aliquote of the sample solution is injected into the titration cell with a syringe (exact sample weight determination by weighing of syringe before and after injection) and the water determination is started. The results must be corrected for the blank value of the solvent.

Coulometry without diaphragm

Reagents:

Working medium
100 mL 109257 Aquastar™ - CombiCoulomat fritless - Coulometric Karl Fischer reagent for cells with or without diaphragm

Titration Parameters:
Default coulometer settings for cell without diaphragm:
For end point indication, e.g.:
I(pol) = 5 - 10 µA, U(EP) = 50 - 100 mV
Stop criterion: drift < 20 µg/min

Sample size:
Solution of 1 g in 50 mL methanol or appropriate solvent mixture

Procedure:
The Karl-Fischer reagent is placed into the titration cell without diaphragm. The coulometer is started and the solvent is titrated dry. After preliminary titration and stabilisation of drift an aliquote of the sample solution is injected into the titration cell with a syringe (exact sample weight determination by weighing of syringe before and after injection) and the water determination is started. The results must be corrected for the blank value of the solvent.

Materials

     
Related Links