The document discusses three main theories of drug dissolution: 1) Diffusion layer/film theory which describes dissolution as a two step process of drug dissolving from the solid to form a saturated film and then diffusing out of the film. The rate of dissolution is given by the Noyes-Whitney equation. 2) Danckwert's/surface renewal theory which accounts for eddies in the solution exposing new surface areas for dissolution. The rate is expressed as the product of the surface renewal rate and concentration gradient. 3) Interfacial barrier model which assumes the reaction at the solid surface is slower than diffusion, making interfacial transport the rate limiting step described by another equation.

1. Theories of Drug Dissolution
I. Diffusion layer model/Film Theory
II. Danckwert’s model/Penetration or
surface renewal Theory
III. Interfacial barrier model/Double barrier
or Limited solvation theory.

2. I. Diffusion layer model/Film Theory :-
• It involves two steps :-
a. Solution of the solid to form stagnant film or
diffusive layer which is saturated with the drug
b. Diffusion of the soluble solute from the stagnant
layer to the bulk of the solution; this is r.d.s in
drug dissolution.

4. • The rate of dissolution is given by Noyes and
Whitney:
= k (Cs- Cb) dc
dt
Where,
dc/dt= dissolution rate of the drug
K= dissolution rate constant
Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the
solution at time t

5. Modified Noyes-Whitney’s Equation -
dC
dt
DAKw/o (Cs – Cb )
Vh
=
Where,
D= diffusion coefficient of drug.
A= surface area of dissolving solid.
Kw/o= water/oil partition coefficient of drug.
V= volume of dissolution medium.
h= thickness of stagnant layer.
(Cs – Cb )= conc. gradient for diffusion of drug.

6. II. Danckwert’s model/Penetration or
surface renewal Theory :-
• Dankwert takes into account the eddies or
packets that are present in the agitated fluid
which reach the solid-liquid interface, absorb
the solute by diffusion and carry it into the bulk
of solution.
• These packets get continuously replaced by
new ones and expose to new solid surface
each time, thus the theory is called as surface
renewal theory.

8. • The Danckwert’s model is expressed by
equation
dC
dt = dm
V = A (Cs-Cb). γ D
dt
Where,
m = mass of solid dissolved
Gamma (γ) = rate of surface renewal

9. 3) Interfacial layer model
S
Film boundary
Bulk solution
Cs
C
Stagnant layer
In this model it is assumed that the reaction at solid surface is not
instantaneous i.e. the reaction at solid surface and its diffusion across the
interface is slower than diffusion across liquid film.
therefore the rate of solubility of solid in liquid film becomes the rate
limiting than the diffusion of dissolved molecules
equation : dm/dt = Ki (Cs – C ) K = effective interfacial transport rate
constant

10. Biopharmaceutical Classification System
High Solubility
(Dose Vol. NMT
250 mL)
Low Solubility
(Dose Vol. >250
mL)
High Permeability
(Fract. Abs. NLT
90%)
CLASS І
e.g. Propranolol
metoprolol
CLASS II
e.g. piroxicam,
naproxen
Low Permeability
(Fract. Abs.
<90%)
CLASS III
e.g. ranitidine
cimetidine
CLASS IV
e.g. furosemide
hydrochlorothiazide