Medicine - API And Dissolution unfinished

Question 1

State the Noyes-Whitney equation and what each letter represents

Answer 1

Dm/dt= [DA(Cs-C)]/h

Dm/dt = The rate of dissolution (Change of mass/time)
D= Diffusion coefficient
A= Surface area of particle
Cs=Saturation concentration in the diffusion layer
C=Saturation concentration in the GI fluid
h= Thickness of the diffusion layer

Question 2

Where does the Noyes-Whitney equation originate from?

Answer 2

Fick law

Question 3

What are sink conditions? Define it mathematically

Answer 3

When the concentration of a particle in the GI fluids is so rapidly removed (e.g. By absorption) that the concentration is near 0 or is 0
Sink conditions are generally when Cs (the concentration in the diffusion layer) is 10 times greater than C (the concentration in the GI fluid)
I.e. Sink conditions when Cs>10C

Question 4

How does the Noyes-Whitney equation differ in sink conditions? Explain this change

Answer 4

It becomes:
Dm/dt= (DACs)/h

C is no longer in the equation because it is=0, or Cs>10C
This means that the particle is being removed from the GI fluid as soon as it is in the fluid

Question 5

Name 4 drug factors that affect the dissolution rate

Answer 5

• Surface area of the particle (hence also particle size)
• Granulation
• Lubricants
• Solubility in the diffusion layer

Question 6

How does the surface area and size of a particle affect its dissolution rate? What can you add to increase the rate?

Answer 6

Particle size influences its surface area.
Increased surface area increases dissolution by increasing porosity.
Dispersibility in the medium also affects dissolution rate
Add a wetting agent (e.g. A surfactant)

Question 7

Why is a particle with low dispersibility bad at dissolution?

Answer 7

If the molecules don’t disperse (e.g. Flour and water), they will agglomerate to release particles. This should be avoided.

Question 8

How do wetting agents work?

Answer 8

They reduce the surface tension, therefore increase the wettability so the solid sinks into the liquid

Question 9

Give 3 examples of drugs where a decreased particle size aids dissolution

Answer 9

Griseofulvin (micronised)
Theophylline
Nitrofurantoin
Digoxin

Question 10

Give 3 examples of drugs where a decreased particle size reduces the dissolution
Also give a type of drug that one should beware of when it comes to surface area/particle size

Answer 10

Aspirin
Phenobarbitone
Phenacetin

Beware of hydrophobic drugs

Question 11

What is granulation?

What affect does granulation have on the dissolution rate?

Answer 11

• Renders the surface of hydrophobic drugs hydrophilic
• May produce viscous layers around drug particles
• May reduce dissolution rates and increase disintegration times as increased viscosity reduces the rate of diffusion

Question 12

What affect do lubricants have on the dissolution rate?

Answer 12

Lubricants may reduce the dissolution rate

Question 13

How does solubility of the drug in the diffusion layer affect the dissolution rate?

Answer 13

Solubility related to molecular interaction
Most drugs are weak electrolytes
-weak acid solubility increases with pH (more soluble in the small intestine)
-weak base solubility decreases with pH (more soluble in the stomach)

Question 14

What is the relationship between the diffusion coefficient and viscosity?

Answer 14

The diffusion coefficient (and hence dissolution) is viscosity dependent.
Increased viscosity leads to decreased diffusion