DIFFUSION
By:
Dina Rahmawanty,[Link]
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WHAT IS DIFFUSION ?
• Diffusion is a process of migration of solute
molecules from a region of higher concentration
to a region of lower concentration and is brought
by random molecular motion.
• Movement from one side of membrane to another
side.
• Diffusion is a time dependent process.
• Movement is based on kinetic energy(speed),
charge, and mass of molecule
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DIFFUSION
It is defined as a process of mass transfer of
individual molecules of a substance brought about by
random molecular motion and associated with a
driving force such as a concentration gradient.
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DIFFUSION BASED PROCESS
Drug absorption
Drug elimination
Drug release
Osmosis
Ultra filtration
Dialysis
Mambrane
Barrier
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STEADY STATE DIFFUSION
A system is said to be steady state , if the condition do
not vary with time
dc/dt or dm/dt
should be constant for diffusion
To described steady state diffusion fick’s I and II laws
should be described
Fick’s first law gives flux in a steady state of flow. Thus it
gives the rate of diffusion across unit cross section in the
steady state of flow.
Second law refers to the change in concentration of
diffusant with time ‘t’ at any distance ‘x’.
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Consider the diffusant/solution originally dissolved in the
left hand compartment of the cell , solvent alone is placed on
the right hand side of the barrier, the solute diffuses through
the central barrier from solution to solvent side.
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FICK´S I LAW
The amount “M” of material flowing through a unit
cross section “S” of a barrier in unit time “t” is known as the
flux “J”
dM
J
S .dt
The flux, in turn, is proportional to the concentration
gradient, dc/dx:
dc
J D
dx
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Diffusion coefficient/ diffusivity
No. of atoms dn dc
crossing area A DA Cross-sectional area
per unit time dt dx Concentration gradient
Matter transport is down the concentration gradient
Flow direction
A
As a first approximation assumed D ≠ f(t)
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J atoms / area / time concentrat ion gradient
dc
J
dx
dc
J D
dx
1 dn dc
J D
A dt dx
dn dc
DA
Fick’s first law
dt dx
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FICK’S SECOND LAW
An equation for mass transport that emphasizes the
change in concentration with time at a definite location
rather than the mass diffusing across a unit area of barrier in
unit time (Fick’s Law I) is known as Fick’s second law
c J
t x
Differentiating the first law expression with respect to
x one obtains
J c 2
D 2
x x
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substituting Dc/dt From the above equation
c 2c
D 2
t x
Its represents diffusion only in x direction
c 2c 2c 2c
D 2 2 2
t x y z
Its represents diffusion in three dimensions (X,Y,Z)
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STEADY STATE (STABLE)
The solution in the receptor compartment is constantly
removed and replaced with fresh solvent to keep the
concentration at low level . This is know as “ SINK
CONDITION ” . The left compartment is source and right
compartment is sink.
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The diffusant concentration In the left
compartment falls and rises in the right
compartment until equilibrium is
attained , based on the rate of removal of
diffusant from the sink and nature of
barrier.
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When the system has been in existence a sufficient time,
the concentration of diffusant in the solution at the left and
right compartments becomes constant , but obviously not
same .
Then within each compartment the rate of change of
concentration dc/dt will be zero and by second law.
dc d 2c
D 2 0
dt dx
Concentration will not be constant but rather is likely to
vary slightly with time, and then dc/dt is not exactly zero.
The conditions are referred to as a “QUASI STATIONARY
STATE” and little error is introduced by assuming steady
state under these conditions. 15
Diffusion through membranes
Steady Diffusion Across a Thin Film and Diffusional
Resistance
• steady Diffusion across a thin film of thickness “h”,
•the concentration of both sides cd&cr kept constant,
•Diffusion occurs in the direction the higher concentration(Cd) to lower
concentration(Cr) the concentration of both sides cd&cr kept constant,
• after sufficient time steady state is achieved and the concentrations are constant at all
points,
•At steady state (dc/dt=0), ficks second law becomes
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Pr o c e d u r e s a nd a ppa r a t u s
a s s e s ing d r u g d if f u s io n
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SIMPLE DIFFUSION CELL
The diffusion chamber constructed in a simple way
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DIFFUSION CELL FOR PERMEATION THROUGH
STRIPPED SKIN LAYERS:
It is developed by wurster et al. to study the diffusion
through stratum corneum of various permeants , including
gases, liquids and gels.
A-glass stopper
B-glass chamber
C-aluminum collar
D-mambrane & sample holder
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BIOLOGIC DIFFUSION
Gastrointestinal absorption of drugs
Drug pass through living membranes according to two
main classes of transport
1) passive transfer
It involves a simple diffusion driven by differences in
drug concentration on the two sides of the membrane.
2)carrier mediated
This is 2types
a)active transport (requires energy)
b)facilitated diffusion(does not depend on energy )
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pH-partition Hypothesis
Biologic membranes are predominantly lipophlic, and
drugs penetrated theses barriers mainly in their molecular,
undissociated form.
drugs are absorbed from the gastrointestinal tract by
passive diffusion depending on the fraction of undissociated
drug at pH of the intestines.
pH-partition principle has been tested in a large number
of in vitro and in vivo studies, and it is only partly applicable
in real biologic systems.
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Transport of a drug by diffusion across a membrane such as the gastrointestinal mucosa
is governed by Ficks law
dM Dm SK
(c g c p )
dt h
Gut compartment has high conc. and a large volume compared to Cp
Cg becomes constant and Cp relatively small
Equation becomes :
dM Dm SKC g
dt h
Where,
M= amount. Of drug in gut compartment at time ‘t’
Dm=diffusivity in intestinal membrane
S= area of the membrane
K= partition coefficient
h= membrane thickness
Cg=conc. of drug in intestinal compartment
Cp=conc. of drug in plasma compartment
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Applications
• Release of drugs from dosage forms diffusion controlled
like sustained and controlled release products.
• Molecular weight of polymers can be estimated from
diffusion process.
• The transport of drugs from gastrointestinal tract, skin
can be predicted from principal of diffusion.
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• Processes such as dialysis, micro filtration, ultra
filtration, hemodialysis, osmosis use the principal of
diffusion.
• Diffusion of drugs into tissues and excretion through
kidney can be estimated through diffusion studies.
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References
‘SINKO .J PATRICK’ , “Martin’s physical pharmacy and
pharmaceutical sciences” , 5th edition , pp no.301 to 337.
‘SUBRAMANYAM.C.V.S’ , “A text book of physical
pharmaceutics” , pp no.-110 to 127.
The theory and practice of industrial pharmacy ,leo
lachmann ,heberta. Liberman ,joseph L. Kanio:3rd edition
,pg no- 158 to 159.
Encyclopedia of pharmaceutical technology , 2nd edition
,volume -2: pg no -1246 to 1247 ; edited by james swarbrick
,james [Link].
[Link]
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