1. Diffusion
(Dr.) Mirza Salman Baig
Assistant Professor (Pharmaceutics)
AIKTC, School of Pharmacy,New Panvel
Affiliated to University of Mumbai (INDIA)
2. Defination
• Diffusion is the processes of mass
transfer of indivisual molecule of a
substance because of random
molecular motion (Brownian motion)
and associated with driving force
such as concentration gradient
4. Application
• Release of drug from dosageform in
diffusion controlled system...SR
• Molecular wt of polymer can be
estimated
• Transport of drug (absorption) from
GIT
• Diffusion of drug in tissues
(distribution) and excretion through
kidnies
• Dialysis/ Microfiltration/ultrafiltration
6. Diffusion through biological
membranes
• Dissolution of drug in polymeric
membrane then simple molecular
diffusion
• Drug + Solvent transport across skin
• Steriodal molecule with hydrophilic
group pass through hair follicles
• Diffusant may pass through pores
• Diffusion play important role in
transport of drug in kidney, brain and
liver
7. • Diffusion through lipoidal membrane
(BBB) is known as transcellular
diffusion
• Paracellular diffusion occurs
through the space between cells
• In addition to drugs, nutrients also
pass through biolofical membranes
Diffusion through biological
membranes
8. • Energy dependent carrier mediated
diffusion through biological
membrane (Active transport)
• Energy independent carrier
mediated diffusion through biological
membrane (Facilitated diffusion)
Diffusion through biological
membranes
9. • Membrane transporters are
specialized proteins that facilitate
drug transport
• Active transport
• Facilitated diffusion
Diffusion through biological
membranes
11. • Concentration gradient
• Osmotic pressure
• Temperature
• Electrical potential
Driving force Diffusion
12. Ficks Law of diffusion
Rate of diffusion=
(surface area × Concentration Gradient) ÷
Thickness of membrane
Vid
13. Measurement of Diffusion
• Diffusion is result of brownian
motion.
• Molecules diffuse spontaneously till
equilibrium is established
• Diffusion of molecules is estimated
using diffusion cell
• Solute is dissolved in solvent is
placed in donor compartment
• Solvent is placed in receptor
compartment
14. Diffusion cell
• Made up of glass or clear plastic
• Easy to assemble and clean
• May be thermostated
• Automatic sample collection from
receptor
• Analysis can be done using
chromatography/ Sprctrometry
16. Steady state diffusion
• System is said to be steady state if
conditions do not vary with time
• Mass transfer remain constant with time
• Concentration of solute in donor and
receptor compartment is maintained
constant
• To acheive this both the compartments
are connected to reserviours of solute
(maintained at respective
concentration) and recirculated.
• Concentration gradient remain constant.
17. Sink condition
• Concentration in receptor
compartment is maintained at
lower level compare to
concentration in the donor
compartment.
• Donor compartment act as source
and receptor compartment act as
sink.
• Receptor compartment is
connected to large resirviour and
solution is recirculated.
18. Flux (J)
• Molecules transport from one
compartment to other over a period
of time.
• i.e. rate of mass transfer dM/dt
• Flux can be expressed as J
• J= 1/S . dM/dt ....(1)
• dM= change in mass, gm
• dt= change in time, sec
• S= Barrier surface area, cm2
19. Ficks First Law
• States that Flux is directly
proportional to the concentration
gradient
• J= -D . dC/dx ...(2)
• D= diffusion coeff
• dC= Change in conc
• dx= change in distance
20. Ficks First Law
• Negative sign represent decrease in
concentration from donor
compartment
• From eqn (1) and (2) we get
• dM/dt = -DS . dC/dx
21. Ficks Second Law
• States that the change in
concentration with time in a
particular region is proportional to
the change in concentration gradient
at that point of time.
• dC/dt = - dJ/dx
22. Ficks Second Law
• From Ficks first law
• J= -D . dC/dx
• Differentiating wrt x
• - dJ/dx = D d2C/dx2
• As we know - dJ/dx = dC/dt
• dC/dt = D d2C/dx2
• Above equation represent diffusion in
x direction only. Extending this to 3
coordinates x y and z
• dC/dt = D [d2C/dx2 + d2C/dy2 + d2C/dz2]
23. Driving forces for diffusion in pharmaceutical systems
Driving Force Example Description
Concentration
Passive
diffusion
Mass transfer due to random motion of
molecule , across concn gradient
Drug
dissolution
Disintegration --> Deaggregation --> Fine
particles--> Diffusion of drug from small
particles--> Dissolution --> Absorption
Pressure
Osmotic
pressure
Osmotic pressure cause controlled release
of drug, osmotic core coated with
semipermiable membrane, orifice for drug
release
Pressure
driven jets
High velocity jet (>100m/s) penetrate skin
and deliver drug subcutaneously or
intramuscularly without needle
24. Driving Force Example Description
Temperature
Lyophilization
Freeze-Drying, of frozen aqueous
solution containing drug
Microwave
Assisted
Extraction
(MAE)
Microwave radiation-> Moisture get
heated up –> Moisture evaporates
–> Generation of tremendous pressure
on cellwall–> Swelling of plant cell
–>Rupture of the cell –>Leaching out
of phyto-constituents
Electrical
Potential
Iontophoretic
dermal drug
delivery
It is used to enhance transdermal
delivery by applying small current
Electrophoresis
Movement of charged particles across
membrane under the influence of
applied potential difference
Driving forces for diffusion in pharmaceutical systems
27. Permeability
• If membrane seperate two
compartments of diffusion cell of cross
sectional area S and thickness h
• If concentration on donor and receptor
sides are C1 and C2 respectively, Ficks
first law will become
• J = dM/dt
= D [(C1-C2)/h]
28. Permeability
• C1 and C2 can be replaced by
partition coefficient multiplied by
concentration on donor (Cd) and
receptor (Cr) side
• K= C1/Cd = C2/Cr
• P= DK/h
• P= Permeability
• K= Distribution coeff
• h= Barrier thickness