dissolution of solids

Question 1

What are the 3 steps to the dissolution of a crystalline drug solution?

Answer 1

STEP 1:
Solute molecule
leaves particle
STEP 2:
Creation of a
cavity in the
solvent
STEP 3:
Solute molecule
enters the cavity

Question 2

Why must the solvent go through diffusion/ mass transport?

Answer 2

Saturation of the
boundary layer happens
almost instantaneously

Solute diffusion from the
boundary layer into the
bulk solvent takes more
time

Question 3

What is the Noyes-Whiteney equation?

Answer 3

dm/ dt = k1 A (CS – C)
h

Question 4

What is the NW equation for?

Answer 4

This process of “mass transfer” change (dm) with time (dt)
effectively determines the rate of dissolution for pharmaceutical
solids, i.e. drugs

Question 5

How can we speed up the dissolution process? (SA)

Answer 5

• Surface area of undissolved solid drug (A)
  – Increasing the surface area will increase the dissolution rate
  – This can be done by reducing the particle size

Question 6

How can we speed up the dissolution process? (Cs)

Answer 6

• Saturated solubility of drug in solvent (CS)
  – Saturated solubility values are fixed – but only when the conditions
  are fixed
  – Increasing the temperature will increase CS (as long as dissolution
  is an endothermic process)
  – Changing the solvent (or adding a second solvent – a “cosolvent”)
  will alter CS
  – Change the drug, e.g. use a salt or a different polymorph

Question 7

How can we speed up the dissolution process (C)?

Answer 7

• Concentration of drug in solution at time t (C)
  – Increase the volume of solvent
  – Remove dissolved drug from the solution

Question 8

How can we speed up the process of dissolution? (K¹)

Answer 8

Dissolution rate constant (k1)
– Primarily affected by the viscosity of the dissolution medium
– Molecular characteristics, e.g. size of molecules, are also important

Question 9

How can we speed up the process of dissolution? (h)

Answer 9

Thickness of boundary layer (h)
– Agitation of the drug in the dissolution medium, e.g. by stirring,
can decrease the thickness of h
– Cannot be altered in vivo

Question 10

How can we determine solubility practically?

Answer 10

• empiracally or experimentally
• consider dissolution medium + conditions
• consider temperature analysis