Pharm Aquametry

Question 1

Define aquametry.

Answer 1

Analytical process to measure the water present in a substance or product.

Question 2

What can happen if pharm substances contains more than the specified/accepted amount of water? (6)

Answer 2

• Enhances degradation of drug by hydrolysis.
• Facilitates growth of microorganisms - spoilage.
• Increases weight of substance complicating batch/formulation calculation.
• Physical properties modified by H2O content.
• Process such as granulation, tableting and coating affected.
• Impairs stability.

Question 3

What is water of crystallisation?

- molecular mass is affected by water of crystallisation.

Answer 3

Water that is stoichiometrically (chemically) bound within the crystal but can dissociate by heating.

Question 4

What 4 processes influence the hydration of a pharmaceutical product?

Answer 4

Efflorescence
Hygroscopy
Deliquescence
Exsiccation

Question 5

What is efflorescence?

Answer 5

The loss of water of crystallisation to the atmosphere on exposure to air.
- depends on vapour pressure.

Question 6

How can efflorescence be prevented?

Answer 6

By closing the container tightly immediately after use and filling the container completely so there is no space for air.

Question 7

What is hygroscopy?

Answer 7

The ability of a substance to attract and hold water molecules from the surrounding atmosphere by absorption or adsorption.

Question 8

Describe how deliquescence works.

Answer 8

If the material is very hygroscopic, it may absorb enough water from the atmosphere to dissolve in this water in a process called deliquescence.
Material = deliquescent.

Question 9

What is exsiccation?

Answer 9

The process of removing water of crystallisation by heating.

Heat is applied until a constant weight is obtained or the calculated loss in weight has taken place.

Question 10

What are the 3 methods used to measure the water content in pharmaceutical product?

Answer 10

1. Drying methods - drying ovens, IR lamps and IR balances.
2. Distillation.
3. Titrations - KF titrations.

Question 11

What is the disadvantage of using drying methods such as ovens to determine the water content of a product?

Answer 11

Loss on drying is determined but not necessarily water content - if containing volatile substances they will be lost.
Time consuming process.

Question 12

What is the disadvantage of using distillation as a method to determine water content?

Answer 12

Large samples required.
Unsuitable for trace amounts of water.
Time consuming.

Question 13

What is the advantage of using KF titration in determining water content?

Answer 13

Rapid and specific for water.
Small sample size required.
Method can be validated and fully documented.

Question 14

What is the disadvantage of using KF titration in determining water content?

Answer 14

Substances which react with iodine/iodide can interfere with the reaction e.g. ascorbic acid and quinine.

Question 15

In what two ways are titration end points detected?

Answer 15

Indicators - phenylphthalein, methyl-orange.
Electrometrically - conductivity, amperometry, potentiometry, voltammetry.

(Others: spectroscopy, calorimetry, pH, precipitation).

Question 16

What is the equivalence point in titration reactions?

Answer 16

Stoichiometrically equivalent amounts of titrant and titrand have reacted and reaction is complete.
- Theoretical end point.

Question 17

What is the end point of a titration reaction?

Answer 17

End point is what is actually measured by indicator or instrumentation.
Is different to equivalence point and there is indicator error.

Question 18

Where does the water come from if the KF reagent is anhydrous?

Answer 18

From the sample itself.

Sample must contain water for reaction to occur.

Question 19

What are the two types of KF titrations called?

Answer 19

Volumetric

Coulometric

Question 20

Describe how the loss on drying process works?

Answer 20

Measure high moisture content in solid/semi-solid materials.
Drying is carried out over potent dehydrating agent = diphosphorus pentoxide granules.
LOD calculated as percentage.
Sample is weighed, dried and reweighed.

Question 21

Why are anhydrous substances sometimes required for certain pharmaceutical formulations?

Answer 21

Reduces bulk and weight of the drug substance/excipient.

Question 22

Explain how vapour pressure works in terms of loss of water into atmosphere etc.

Answer 22

If vapour pressure of the hydrated substance is greater than the vapour pressure of the atmosphere, then the hydrated substance will lose water to the atmosphere and become less hydrous.
The loss of water will continue until equilibrium has been reached between the hydrated substance and atmosphere.

Question 23

What is the gold standard method of detection in KFT?

Answer 23

Amperometry

Question 24

Is LOD method suitable for all pharma products?

Answer 24

Not suitable for pharmaceutical products containing other volatile substances.

Question 25

What apparatus is used to measure the amount of water distilled from sample?

Answer 25

Dean and Stark trap.

Question 26

What conditions are required for LOD approach for water determination?

Answer 26

Materials dried over a drying agent = diphosphorus pentoxide granules and one of the procedures.

• at room temperature and pressure.
• under vacuum (1.5 kPa to 2.5 kPa) at RT.
• under vacuum (1.5 kPa to 2.5 kPa) over a specified temperature range as prescribed by BP monograph.
• under high vacuum (≤0.1 kPa) at the temperature prescribed in BP monograph.