Merits and Limitations of Water determination methods in Pharmaceutical products

Merits and Limitations of Water determination methods in Pharmaceutical products
Karl FIscher Titration
Karl Fischer Titrator

Water can be present in pharmaceutical products in either chemically bound or free state. Differences between moisture content, water of hydration and water activity have been discussed earlier.

In addition to water residual solvents get introduced in active pharmaceutical ingredients due to contact during manufacture or final purification when crystallization in different solvents is carried out.

Loss on drying (LOD) and Karl Fischer titration are two commonly used methods for the determination of moisture in pharmaceutical products.

Loss on Drying (LOD)

It is a common misconception that loss on drying provides the water content of a product. This is not always true as loss on drying gives weight loss due to evaporation of water along with all other volatile components present in the sample. In case of high purity compounds which have insignificant levels of other volatile impurities the weight loss can be a close approximation to the water content though heating may not release all the volatile impurities and water which is bound as water of crystallization.

Limitations of LOD method

  • Temperature and duration of heating of the sample is limited by its melting point and its thermal stability
  • It gives a total of water and volatile residual solvents and is not specific to water alone
  • Heating may not release all the residual solvents or water bound as water of crystallization
  • LOD results are dependent on drying time which has to be specified for each and every product
  • LOD results can be affected by exposure to the environment and accuracy of weighing

Karl Fischer Titration  method

Karl Fischer titration method is highly specific and selective to water and gives the total water present ,i.e, surface absorbed water as well as water of crystallization.

The method is based on a potentiometric determination involving quantitative reaction of water with iodine in presence of an alcohol, a base and sulphur dioxide. Pyridine or less toxic imidazole is used as base along with methanol or ethanol as the alcohol. The Karl Fischer titration method being highly specific and selective to water is free from interference of residual solvents as well as other limitations of the Loss on drying method. Further it is useful for determinations ranging from percentage to ppm levels. The only limitation of the method is the limited solubility of some products in alcohol or their reactivity with Karl Fischer reagent.

Please do share your experiences and offer your comments.

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