Aquametry

Md.Al-Mamun Lecturer Department of Pharmacy Stamford University Bangladesh

Aquametry
Aquametry can be defined as the quantitative determination of water. The determination of water is one of the most important and most widely practiced analysis in pharmaceutical industry.

Importance of water determination

Quantitative determination of water is important because many drugs contain water: As a solvent. (E.g. H2O in Syrup, Suspension or Emulsion) As absorbed water (E.g. Absorbed H2O by Powder for Suspension) As water of crystallization (E.g. Crystals of salts containing H2O) As an adulterant (E.g. Excess Water in Digitalis Leaves)

Physical properties of a drug or a raw material are modified by its water content. Pharmaceutical procedures of granulation, tablet formation & coating operations are affected by water content.

Physical methods of water determination

a) Thermal method: The technique includes the loss of weight by drying. Both the BP and USP describe such measurement under the general term loss on drying. The limitation of this method is that such method also involve losses resulting from other volatile materials or from decomposition. These measurement can be made more specific by limiting the decomposition effects at lower temperature, that is, drying accomplished at reduced pressure. Interference by other volatile materials can often be controlled by a process of measuring the increase in weight of an absorbent selective for water.

Absorption agents used for this purpose are:

Dehydrite (anhydrous magnesium perchlorate) Drierite (calcium sulphate)

Phosphorous pentaoxide
Barium oxide Calcium chloride Anhydrous silica gel An inert gas is allowed to carry the water lost from a known quantity of sample to the absorbent whose gain in weight is then determined.

Azeotrope A mixture of two liquids that boils at constant composition; i.e. the composition of the vapor is the same as that of the liquid known as azeotrope. Chloroform and acetone Alcohol and water Water (100o C) and toluene (110.6o C) form an azeotrope with bp 84.1o C, the azeotrope contains 19.6% water.

Azeotropic distillation method 1. A known weight of sample is placed in a flask with an organic solvent such as xylene or toluene. 2. The flask containing the sample and the organic solvent is attached to a condenser and the mixture is heated.

The organic solvent must be - insoluble with water; - have a higher boiling point than water;

- be less dense than water; and

- be safe to use.

Azeotrope 3. The water in the sample evaporates and moves up into the condenser where it is cooled and converted back into liquid water, which then trickles into the graduated tube. 4. When no more water is collected in the graduated tube, distillation is stopped and the volume of water is read from the tube.

b) Azeotropic distillation method (Dean and Stark trap): The usual procedure is to add a water immiscible solvent to the material containing moisture (water) and in this manner to co-distill any water present.

Recondensation of the vapors results in separation of water from the immiscible solvent making it available for volumetric measurement. The hydrocarbons benzene, toluene and xylene are the solvents usually used in this determination.

These solvents with a specific gravity less than 1 (or density less than water), have the added advantage of allowing the water to form a layer at the bottom of the Dean and Stark trap, where it can be measured directly.

Fig: Dean - Stark apparatus

Reflux condenser

Dean-Stark apparatus

Glass flask

Fig: Apparatus for azeotropic distillation method

Azeotropic distillation determination of moisture have extensive applications because of their, simplicity, economy, efficiency and accuracy. The method is specially successful for moisture determination in bulk materials, such as plant parts and for medicinal soap solutions.

The main disadvantage to this procedure is that relatively large samples are required, making the technique unsuitable for trace amount of water in expensive pharmaceutical materials.

Chemical methods of water determination

Karl Fischer titration

In 1935, German Chemist Karl Fischer described a specific titrimetric method for the determination of water, remains the most generally applicable procedure.
Karl Fischer titration is a widely used analytical method for quantifying water content in a variety of products. The fundamental principle behind it is based on the Bunsen Reaction between iodine and sulfur dioxide in an aqueous medium. 2H2O + SO2 + I2 H2SO4 + 2HI

Composition of Karl Fischer reagent (USP) Karl Fischer reagent is a mixture ofIodine Anhydrous pyridine Anhydrous methanol Liquid sulfur dioxide 125 170 670 100 gm ml ml ml

In recent years, pyridine, and its objectionable odor, have been replaced in the Karl Fischer reagent by other amines, particularly imidazole. These pyridine-free reagents are available commercially for both volumetric and coulometric Karl Fischer procedures.

1 ml of Karl Fischer reagent when freshly prepared will react with about 5 mg (or 3-6 mg) of water.
When prepared it is general practice to increase the stability of the reagent by adding sulfur dioxide to a stock solution of the other components the day before actual use. Numerous side reactions may occur among the constituent substances. Freshly prepared reagent therefore has a strength about 80% of the theoretical value, but this rapidly falls to about 50% in 1 month and 40% in 3 months.

Chemistry of the reaction In the presence of water, iodine will be reduced and sulfur dioxide oxidized in the following manner: H2O + I2 + SO2 2HI + SO3

The reversibility of the reaction can be prevented by using large quantity of pyridine. The concentration of pyridine is sufficiently large so that I2 and SO2 are complexed with the pyridine as C5H5N I2 & C5H5N SO2. C5H5N I2 + C5H5N SO2 + H2O + C5H5N 2 C5H5N HI + C5H5N SO3
rapid

------------ (1)

The pyridine sulfur trioxide (pyridinium sulfite) compound, an inner salt, reacts, in turn, with the methanol present to form the pyridine salt of methyl sulfate.

C5H5N SO3 + CH3OH

C5H5N+(H)-SO4CH3
------------- (2)

Thus, methanol prevent the further reaction of C5H5N SO3 with water. C5H5N SO3 + H2O C5H5N+(H)-SO4H

The last reaction is undesirable because it is not specific for water. It can be prevented by using excess amount of methanol.

The primary reaction (1) occurs rapidly and permits the direct titration of any available water with the reagent. Karl Fisher determination can be performed by direct titrations or excess of the reagent can be added and the excess can be back titrated with a standard water-in-methanol solution.

For a direct titration, methanol is added to dissolve the sample or to assist in the penetration of an insoluble sample. In back titration procedure, the reagent alone often serves this purpose.

Classification of Karl Fischer Titration

Karl Fischer Titration can be of 2 type 1. Volumetric Karl Fischer Titration 2. Coulometric Karl Fischer Titration Volumetric Karl Fischer Titration
Volumetric Karl Fischer Titration can be defined as a method of titration where an exact volume of Karl Fischer Reagent is consumed during the course of titration from which equivalent amount of Water present in the sample can be detected; i.e. 1 ml of Karl Fischer Reagent is equivalent to 5 mg (or 3 6 mg) water. End point in this titration is detected by color change in the solution.

Volumetric Karl Fischer Titration can be of 2 type

1. Volumetric Karl Fischer Direct Titration 2. Volumetric Karl Fischer Back Titration

Purpose of Performing Volumetric Karl Fischer Titration

Volumetric Karl Fischer Titration is performed when the sample is not colored.

Volumetric Karl Fischer Direct Titration In Volumetric Karl Fischer Direct Titration, sample is dissolved in excess anhydrous methanol and the solution is then filtered to remove impurities. Then, Karl Fischer Reagent is added to the solution drop by drop with the help of a burette; thus, forming a pale yellow solution. When all of the H2O present in the solution will react with Karl Fischer Reagent, the color of the solution will suddenly change into Dark Brown from pale yellow; thus indicating the End Point of the Titration.

Volumetric Karl Fischer Direct Titration

Volumetric Karl Fischer Back Titration

In Volumetric Karl Fischer Back Titration, at first the sample is mixed with excess Karl Fischer Reagent giving the solution a Dark Brown color of excess Karl Fischer Reagent, since all of the water in the sample has already reacted with the Karl Fischer Reagent. Then, A Standard Water in Methanol is added drop by drop to the solution with the help of burette. When all of the H2O in Methanol reacts with Excess Karl Fischer Reagent, the color of the solution will suddenly change into Pale Yellow from Dark Brown; thus indicating the End Point of the Titration.

Purpose of Performing Volumetric Karl Fischer Back Titration

Purpose of Performing Volumetric Karl Fischer Back Titration is to determine the accuracy of the Volumetric Karl Fischer Direct Titration. After the reaction in Volumetric Karl Fischer Direct Titration is complete, the excess amount of Karl Fischer Reagent is determined by titration with a standard H2O in Methanol Solution. The Actual Amount of Karl Fischer Reagent reacting with desired amount of Water is calculated by subtracting the volume consumed in the Back Titration from the volume added in the Direct Titration.

Coulometric Karl Fischer Titration

Coulometric Karl Fischer Titration can be defined as a method of titration where an exact volume of Karl Fischer Reagent is consumed during the course of titration from which equivalent amount of Water present in the sample can be detected; i.e. 1 ml of Karl Fischer Reagent is equivalent to 5 mg (or 3 6 mg) water. End point in this titration is detected by sudden change in the electricity current flow. Coulometric Karl Fischer Titration can be of 2 type 1. Coulometric Karl Fischer Direct Titration 2. Coulometric Karl Fischer Back Titration

Instrument

The Coulometric Karl Fischer Titration vessel is fitted with 1.5 2.9 V Dry cell across a variable resistance of about 2000 which is in series with two platinum electrodes and a microammeter, mechanical stirrer and a burette

Burette

Dry cell

Resistance

 Purpose of Performing Coulometric Karl Fischer Titration Coulometric Karl Fischer Titration is performed when the sample is colored. As a result the End Point cannot be detected by color change.

Coulometric Karl Fischer Back Titration

End point detection

An end point in a Karl Fischer titration can be observed visually based on the color change from pale yellow to dark brown color of the excess reagent (volumetric titration).
An amerperometric or electrometric detection of the Karl Fisher titration end point is employed and found useful specially when the sample is colored (coulometric titration). Under these conditions of constant low voltage with the direct titration procedure, there is a small constant residual flow of current until the end point is reached, accompanied by a large increase in current.

Thus, when water is titrated with the Karl Fisher reagent there is a kick-off or major deflection in the microammeter to indicate the end point when last drop of excess Karl Fisher reagent enter the titration flask. Conversely, when a back titration is employed, there is a sudden drop in current or a dead-stop end point occurs.

Up to the end point in the direct titration of water with Karl Fisher reagent, there are iodide ions present but no free iodine.

At the potential used, the system is irreversible and the electrodes are polarized, that is, they have an impressed potential with a little flow of current.
However, as the free iodine enters the system there is a reversible iodineiodide couple established with the depolarization of electrodes and an increase in the flow of current.

Limitations

The Karl Fischer reagent is highly specific for water but there are some limitations Compounds which react with either iodine or iodide will interfere the process. For example, ascorbic acid will be oxidized by the iodine present in the reagent.

Carbonyl compounds under the conditions of the Karl Fischer determination react with methanol with the formation of acetals or ketals and the liberation of water. R2CO + 2CH3OH R2C(OCH3)2 + H2O
The optimal pH range for the Karl Fischer reaction is from 5 to 8, and highly acidic or basic samples need to be buffered to bring the overall pH into that range.

Advantage of analysis The popularity of the Karl Fischer titration is due in large part to several practical advantages that it holds over other methods of moisture determination, including:

* * * * * *

High accuracy and precision Selectivity for water Small sample quantities required Easy sample preparation Short analysis duration Nearly unlimited measuring range (1ppm to 100%)

Advantage of analysis * Suitability for analyzing: o Solids o Liquids o Gases * Independence of presence of other volatiles * Suitability for automation In contrast, loss on drying will detect the loss of any volatile substance.

Reference: Karl Fischer titration. (n.d.) In Wikipedia, the free encyclopedia online. Retrieved from http://en.wikipedia.org/wiki/