Solubility of Drugs 1

Question 1

Importance of solubility?

Answer 1

A drug must be able to pass the GIT to have therapeutic effect.

Question 2

What is a solution?

Answer 2

Mixture of at least 2 components. A system in which molecules of solute are dispersed in a solvent vehicle.

Question 3

What is a solute?

Answer 3

Drug/active substance

Question 4

What is a solvent?

Answer 4

Vehicle e.g. water, syrup etc. (can be complex)

Question 5

What is solubility?

Answer 5

The extent to which molecules are transferred from solid -> liquid (dissolution)

The maximum amount of a chemical substance at a given temperature/pressure that you can have at equilibrium

Question 6

Relation to concentration?

Answer 6

Solubility of a chemical substance = concentration

Solubility is the maximum concentration you can have at a given set of experimental parameters

Often defined in ‘parts per solvent’

Question 7

In terms of the components that make up a solution - what factors do you need to consider at the beginning of research?

Answer 7

You have a solid drug and a liquid solvent.

Solid drug: most likely a crystal, consider interactions/forces

Liquid solvent: consider interactions/organisation

Question 8

Describe briefly the 3 steps of solubilisation

Answer 8

1. Removal of solute molecule - breaking forces
2. Break forces in liquid to create a ‘cavity’
3. Insertion of the solute molecule into the solvent cavity (requires forces to keep solute in solution)

Question 9

What are some factors affecting solubility? (7)

Answer 9

1. Solid state of the drug i.e. amorphous, crystalline
2. Polymorph type
3. Composition of aqueous media
4. pH
5. Ionic strength of solution
6. Temperature
7. Salts + counter ions (common effect)

Question 10

What is a co-solvent?

Answer 10

Can be used to increase solubility of a poorly soluble drug to reach therapeutic effect

Related to miscibility - ‘like dissolve like’

Question 11

What is miscibility?

Answer 11

The solubility of one liquid in another liquid

Can be immiscible (oil/water), partially miscible (water/phenol) or miscible

Question 12

Most co-solvents are toxic. List the limited list of non-toxic solvents (6)

Answer 12

Water, ethanol, glycerin, PG, PEG, sorbitol

Question 13

Concept of the method of improving solubility? And how is it done?

Answer 13

Create a system of ‘optimum polarity’

Mix solvents with different polarities to solubilise an API (active pharmaceutical ingredient)