 INTRODUCTION:

Drug is the single chemical entity present in a medicine that

is used for diagnosis, prevention, treatment/ or cure of disease.

Dissolution is a process in which a solid substance

solubilizes in a given solvent i.e. mass transfer from the solid
surface to the liquid phase.

Drug dissolution mainly occurs in stomach & intestine.

ACIDIC ENTERIC –
DRUGS ARE COATED
USED TABLETS
 DESCRIPTION:
There are many theories to explain drug dissolution. The
important ones are ----

1. Diffusion Layer model / Film theory

2. Danckwert’s model / Penetration or Surface Renewal
Theory
3. Interfacial barrier model / double-barrier or Limited
solvation theory.
 Diffusion Layer Model / Film Theory:
Simplest & most common theory of dissolution.
This process of dissolution of solid particles in a liquid in
absence of chemical forces, consists of two consecutive
steps------
I. Solution of liquid to form a thin film or layer at the
solid-liquid interface known as Stagnant film or
diffusion layer.

This layer is saturated with the drug.

This step is usually rapid.

II. Diffusion of the soluble solute from the stagnant layer to bulk of the solution.

This step is slower

Rate – determining step in drug dissolution.

 This theory is controlled by Noyes & Whitney equation:

dC/dt = k ( Cs – Cb )

Where,
dC/dt = dissolution rate of the drug
k = dissolution rate constant ( first order )
Cs = concentration of drug in the stagnant layer ( also
called as the saturation or maximum drug solubility )
Cb = concentration of drug in the bulk of the solution at
time t.
 Nernst & Brunner incorporated Fick’s first law of diffusion &
modifies the Noyes-Whitney’s equation to:

dC/dt = DAKw/o (Cs-Cb)/Vh

Where,
D=diffusion coefficient of the drug
A=surface area of the dissolving solid
Kw/o =water in oil partition coefficient of the drug or intrinsic
dissolution rate constant.
Cs-Cb =concentration gradient for drug of diffusion.
V=volume of dissolution medium
h=concentration gradient for diffusion of drug
 Noyes-Whitney’s equation assumes that the surface area
of the dissolving solid remains constants during dissolution
which is practically not possible.

 To account for the particle size decrease & change in

surface area by Hixon & Crowell’s cubic root law of
dissolution is used:

W01/3 – W1/3 = Kt
Where,
W0 =original mass of the drug
W =mass of the drug remaining to dissolve at time t
K =dissolution rate constant
 Modified Noyes & Whitney’s equation represents first order kinetics,
the driving force for which is the concentration gradient (Cs-Cb).

To obtain good in vitro- in vivo dissolution rate correlation , in vitro- in vivo

dissolution must be performed under sink condition. That means Cs >> Cb .

dC/dt = K

This equation follows Zero order kinetics. This represents that dissolution
rate is constant under sink condition.
 Danckwert’s model:
Dankwert didn’t approve of existence of stagnant layer & suggested
that turbulence in the dissolution medium exists at solid/liquid interface.
Danckwert’s model is expressed by-----------
V dC/dt = dm/dt = A( Cs – Cb ) γD
Where,
m=mass of solid dissolved,
γ=rate of surface renewal
 Interfacial barrier model:
An intermediate concentration can exist at the interface
as a result of solvation mechanism & is a function of
solubility rather than diffusion.
This concept is given by------
G = Ki (Cs – Cb )
Where,
G=dissolution rate per unit area,
Ki =effective interfacial transport constant.
 Conclusion:
The diffusion layer model & Danckwert’s model were based on----
 The rate-determining step that controls dissolution is the mass
transport.
 Solid-solution equilibrium is achieved at the solid/liquid interface.

The interfacial barrier model can be extendeded to both diffusion

layer model & Danckwert’s model
 References:
 D.M.Brahmankar & Sunil B. Jaiswal, Biopharmaceutics &
Pharmacokinetics- A treatise, 2nd Ed., Vallabh Prakashan,
Absorption of Drugs, Theories of Drug Dissolution, Page no: 29 -
35.
 V. Venkateswarlu, Biopharmaceutics & Pharmacokinetics, 2nd
Ed., Absorption of a weak acidic drug, Theories of Drug
Dissolution, Page no: 33-36