Diffusion & Dissolution

Dr. Mohammad Shariare

Assistant professor
North South University
Diffusion

Diffusion is the process of spontaneous migration of solute

molecules from a region of higher concentration (i.e., high
chemical potential) to a region of lower concentration (i.e., lower
chemical potential) until the concentration (i.e., chemical
potential) is uniform throughout the system

• The process of diffusion can be studied by observing the flow of

molecules (e.g., drug particles) through a barrier such as polymeric
membrane.
• The passage of solute molecules through the barrier occurs either by
simple molecular diffusion or by movement through the pores and
channels
• Simple molecular diffusion involves dissolution of the solute in the
bulk membrane, whereas the passage through the pores and channels
involves the movement of solute molecules through the solvent filled
pores of the membrane
Fick's First Law of Diffusion
Fick's first law states that the rate of diffusion of a solute
molecule through a barrier is proportional to the concentration
gradient.
J is the flux of a component
dm
J ═ diffusion of the
dt component ex­pressed
in terms of amount
dc (dm) transported in
═ D time (dt) across a plane
dx of unit area

D Is the diffusion coefficient

Diffusion Study
A number of apparatuses have been described for
studying the diffusion of drugs across mem­branes. A
simple cell for the purpose is shown in Fig.
The apparatus consists of two cells A and B separated by
a barrier through which diffusion can occur. The
chambers are generally of glass or clear plastic and are
easy to assemble and clean. This also allows for the
visualization of the liquids and of the rotating stirrers.
The chambers can be thermostated and automatic
sampling devices can also be attached to them.

The drug solution is taken in the donor compartment

while the solvent is taken in the receptor compartment.
Sample solutions are collected periodically from the
receptor compartment and analyzed
spectrophotometrically.
DISSOLUTION
Dissolution may be defined as the process by which a
solid solute enters into solution when added to an
appropriate solvent. Dissolution rate refers to the rate at
which the solid dissolves in a solvent.
 
When a solid dosage form such as a tablet is introduced
into water, the drug contained in the tablet begins to
pass into solution. Simultaneously, the solid matrix of
the tablet disintegrates into granules and these granules
in turn deaggregate into fine particles. Dissolution of the
drug takes place both from the disintegrated granules
and from the fine particles
The rate of dissolution of a solid in a liquid is
quantitatively given by the Noyes-Whitney equation :

dc/dt is the rate of dissolution

D is the diffusion coefficient

S is the surface area of the

exposed solid

V is the volume of the solution

h is the thickness of the diffusion

layer
Cs is the solubility of solid drug

C is the solubility of the drug at

time t
 Dissolution Study
In-vitro methods -

USP Apparatus 1 (Basket) USP Apparatus 2 (Paddle)

 Dissolution Study

• 4o mesh stainless steel basket or paddle attached to the stirring shaft

• Rotation speed specified (e.g.- 50/100 rpm)
• Dissolution fluid either water, buffer solution or dilute acid solution
simulating the gastric pH
• Temperature maintained at 370C
• Sample withdrawn different time interval according to methods in USP/BP
• The volume of dissolution fluid is maintained constant by replacing the
amount of sample removed with fresh dissolution media
• Then determine the dissolution rate
• USP apparatus 1 is used for capsule dosage form which tend to float,
whereas apparatus 2 is for non floating dosage form
 Dissulution study
• Drug release or transport is mainly occur by dissolution
and diffusion mechanism
• Where the rate of drug transport is dependant on-
1. The physicochemical properties of drug
2. The nature of the membrane
3. The concentration of drug across the membrane