Dissolution of solids

Question 1

Dissolution meaning

Answer 1

Occurs when attractive forces between the molecules in two different solutions are greater than the molecules within one solution

Question 2

The steps of dissolution mechanisms

Answer 2

1. Solute molecule leaves particle
2. creation of the cavity in the solvent
   solute molecule enters the cavity

Question 3

Saturation - dissolution mechanisms

Answer 3

• Layer around the boundary layer - happens almost instantaneously

Question 4

Boundary layer (h)

Answer 4

Cs

Question 5

Saturation layer

Answer 5

C

Question 6

Process when molecules of solute move from boundary layer into the bulk solvent

Answer 6

Process of diffusion - “mass transfer”

Question 7

Noyes-Whitney equation =

Answer 7

dm/dt = k1A(Cs-C)/h

Determines the rate of dissolution for pharmaceutical solids

Question 8

What happens if equation value increases?

Answer 8

Rate speeds up

Thicker boundary layer = takes longer to defuse

(Cs - C) term in bracket increases = rate increases

Question 9

dm/dt = k1A (Cs-C)/h. meaning

Answer 9

k1 = dissolution rate constant
A = surface area of dissolved solid drug
Cs = saturated solubility of drug in solvent (dissolution medium)
C = concentration of drug in solution at time (t)
h = thickness of boundary layer

Question 10

How can the dissolution process speed up?

Answer 10

Increasing surface area - reduce particle size

1 block = 216 (6x6x6)
8 block = 432 (3x3x6x8)

Question 11

Saturated solubility of drug in solvent (Cs)

Answer 11

Normally fixed - only when conditions are fixed

Question 12

Increase temp - effect on Cs?

Answer 12

increase (as long as dissolution is an endothermic process)

Question 13

Changing the solvent or adding “cosolvent” (another solvent) - effect on Cs

Answer 13

It will alter Cs

Change the drug e.g use a salt or a different polymorph

Question 14

Concentration of drug in solution at time t (C)

Answer 14

• Increase the volume of solvent
• Remove dissolved drug from the solution

Question 15

Dissolution rate constant (k1)

Answer 15

-primarily affected by the visocity of dissolution medium
- molecular characteristics e.g size of molecules

Question 16

Thickness of boundary layer (h)

Answer 16

• Agitation of the drug in the dissolution medium, e.g by stirring can decrease the thickness of h
• Cannot be altered in vivo

Question 17

Step 1 - determine solubility practically

Answer 17

• Drug and solvent should be pure as possible
  -Solution will be span with a MAGNETIC STIRRING BAR
• keep temp constant (in oven/ cupboard) e.g human body temp - 37C
• RESULTS: if solution is STILL clear - it is NOT saturated
• wait for solution to turn cloudy

Question 18

Step 2 - determine solubility practically

Answer 18

2. Filter OR Centrifuge - any solids will fall to bottom (pellets) - Centrifuges has power to keep temp constant

Question 19

Step 3 - determine solubility practically

Answer 19

3. Analysis = UV spectronomiter. Light goes through to see what is the content of the solution.
   More light that is absorbed mean more drug that needed to saturate the solution.

Question 20

How to control the experiment

Answer 20

• in an oven = controlled temprature
• e,g human body temp - 37C
• important = keep it constant

Question 21

Calibration curve **graph

Answer 21

Determines the unknown drug concentration through the known Absorbance recorded in the UV sp

Question 22

Calibration curve **graph

Answer 22

Determines the unknown drug concentration through the known Absorbance recorded in the UV spectrometer