Pre-formulation - Solubility

Question 1

What is displacement?

Answer 1

• volume of solution that’s displaced /changed by a dissolving solid as the solid enters the solution
• water shell forms around it, water molecules move
• results in increase in volume

Question 2

What is solubility?

Answer 2

• Concentration of a solute in a solution at saturation

Question 3

What is saturation?

Answer 3

• point at which no additional solute can be added to a solution
• equilibrium point

Question 4

What is Ksp ?

Answer 4

• Solubility product constant
• Ksp = [products] / 1
• 1 = reactant (not included cause it is solid)

Question 5

What factors affect solubility?

Answer 5

• Temperature
• pH
• pressure

Question 6

Why is solubility important in our body?

Answer 6

• Important for drug absorption
• drug only active when dissolved and absorbed

Question 7

What is the role of temperature in drug solubility?

Answer 7

• Higher temperature increases solubility
• but not for all drugs

Question 8

What classifies something as soluble ?

Answer 8

• If it dissolves completely in 250ml

Question 9

What is the Biopharmaceutics Classification System (BCS)?

Answer 9

• system that categorizes drugs based on solubility and permeability to help inform formulation strategies.

Question 10

How can solubility of a drug be enhanced?

Answer 10

• salt formation
• pH adjustment,
• complexation
• addition of solubilizing agents.

Question 11

what does the term ‘ionization’ refer to in solubility?

Answer 11

• drug molecule gains or loses protons
• can enhance solubility in aqueous solutions.

Question 12

How does the crystalline structure of a drug affect its dissolution?

Answer 12

• molecules are tightly packed by intermolecular bonds
• these bonds must break during dissolution

Question 13

Why can different crystalline forms of the same drug have different properties?

Answer 13

• bonds result in different packing arrangements
• different packing arrangements can result in different properties eg. solubility

Question 14

As substances dissolve in a solvent the volume of the solution
can increase. Considering this fact, is it better to use mol/kg
(molality) or mol/L (molarity) for solubility measurements ?

Answer 14

• better to use molality (mol/kg)
• because mass of solute stays constant regardless of change in volume

Question 15

Name and briefly describe 5 ways of solubility enhancement by
formulation design.

Answer 15

• increasing temperature
• increasing pressure
• salt formation
• complexation = form complexes with cyclodextrins, which enhance their solubility
• pH Adjustment = can improve ionisation which improves solubility

Question 16

What is meant by the ‘boundary layer’ in dissolution?

Answer 16

• thin layer on the surface of a dissolving solid
• the drug concentration is at saturation
• before diffusing into the bulk solution.

Question 17

what is mass transport ?

Answer 17

• movement of drug molecules from concentrated boundary layer into bulk fluid

Question 18

Buffering and Drug Dissolution (Aspirin Example)

Answer 18

• salts buffer boundary layer, increasing drug solubility
• aspirin solubility enhanced at alkaline pH (becomes ionised)
• ionised drugs dissolve faster than un-ionised drugs
• buffering does not change pH of the bulk solution
• aspirin may precipitate back out after dissolving

Question 19

What is supersaturation?

Answer 19

• contains more solute than under normal equilibrium conditions due to cooling/evaporation
• unstable solution so precipitation takes place

Question 20

What is Ficks 1st law?

Answer 20

• How fast do substances diffuse

Question 21

What is Ficks 2nd law ?

Answer 21

• Time to reach concentration at point X