Solubility [Dr Green]

Question 1

Define: Solution

Answer 1

A liquid mixture in which the minor component (the solute) is uniformly distributed within the major component (the solvent)

Question 2

Define: Solvation (hydration)

Answer 2

Process of binding solvent to solute

Question 3

Define: Drug dissolution

Answer 3

Spontaneous dissolving effected by:
Molecular structure of the solute
Additives’ interactions with solvent and solute

Question 4

List 5 factors which influence solubility

Answer 4

Surface area
Boiling or melting point
Functional groups of solute
Crystal properties (electrolytes)
pH

Question 5

List 4 factors which impact on the rate of dissolution

Answer 5

Crystallinity (crystalline vs amorphous)
Particle size
Agitation
Temperature

Question 6

Why are acidic drugs less soluble in acidic solutions?

Answer 6

As the predominant unionised form cannot interact with water

Question 7

Why are basic drugs more soluble in acidic solutions?

Answer 7

The ionic form is predominant so can interact with the water in the solution

Question 8

Which forms of molecule exist in weak acids?

Answer 8

For weak acids, both ionised and unionised forms are present at equilibrium in the solution

Question 9

Which form of molecule has a greater solubility - ionised or unionised?

Answer 9

Ionised

Question 10

How do buffers work in a solution?

Answer 10

Buffers stabilise pH and determine the degree of disassociation

Question 11

What is the % ionised of a basic solution at a low and pHs?

Answer 11

100% ionised basic solution at low pH

0% ionised at high pH

Question 12

What is the % ionised of an acidic solution at low and high pHs?

Answer 12

0% ionised at low pH

100% ionised at high pH

Question 13

List 3 tactics to improve solubility

Answer 13

Co-solvency = altering polarity of solution
Salt forms and changing pH
Solubilisation = use of surfactant micelles to improve solubility

Question 14

What is the purpose of cyclodextrins?

Answer 14

Hydrophobic inside and hydrophilic outside
Forms complexes with hydrophobic molecules
= improves solubility and bioavailability

Question 15

List 4 techniques that scientists can use to improve a poorly soluble API

Answer 15

Polymorph screen = find crystalline forms of the API by crystallisation
Salt screen = makes salts of the API - find the one with the best properties
Make amorphous = by freeze drying or spray drying
Form a co-crystal = convert API from one crystalline form to another by crystallising it out of solution with an inactive molecule