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Diffusion
(Dr.) Mirza Salman Baig
Assistant Professor (Pharmaceutics)
AIKTC, School of Pharmacy,New Panvel
Affiliated to University of Mumbai (INDIA)
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
Diffusion
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
Application
Dissolution of drug from
• Tablet
• Powder
• Granules
• Ointment
• Suppositories
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
• 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
• Energy dependent carrier mediated
diffusion through biological
membrane (Active transport)
• Energy independent carrier
mediated diffusion through biological
membrane (Facilitated diffusion)
Diffusion through biological
membranes
• Membrane transporters are
specialized proteins that facilitate
drug transport
• Active transport
• Facilitated diffusion
Diffusion through biological
membranes
Diffusion through biological
membranes
• Concentration gradient
• Osmotic pressure
• Temperature
• Electrical potential
Driving force Diffusion
Ficks Law of diffusion
Rate of diffusion=
(surface area × Concentration Gradient) ÷
Thickness of membrane
Vid
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
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
Diffusion cell
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.
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.
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
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
Ficks First Law
• Negative sign represent decrease in
concentration from donor
compartment
• From eqn (1) and (2) we get
• dM/dt = -DS . dC/dx
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
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]
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
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
Electrophoresis
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]
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

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Diffusion

  • 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
  • 5. Application Dissolution of drug from • Tablet • Powder • Granules • Ointment • Suppositories
  • 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
  • 25.
  • 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