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Diffusion and Ficks Law

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  1. 1. Diffusion (Dr.) Mirza Salman Baig Assistant Professor (Pharmaceutics) AIKTC, School of Pharmacy,New Panvel Affiliated to University of Mumbai (INDIA)
  2. 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
  3. 3. Diffusion
  4. 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. 5. Application Dissolution of drug from • Tablet • Powder • Granules • Ointment • Suppositories
  6. 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. 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. 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. 9. • Membrane transporters are specialized proteins that facilitate drug transport • Active transport • Facilitated diffusion Diffusion through biological membranes
  10. 10. Diffusion through biological membranes
  11. 11. • Concentration gradient • Osmotic pressure • Temperature • Electrical potential Driving force Diffusion
  12. 12. Ficks Law of diffusion Rate of diffusion= (surface area × Concentration Gradient) ÷ Thickness of membrane Vid
  13. 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. 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
  15. 15. Diffusion cell
  16. 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. 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. 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. 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. 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. 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. 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. 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. 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. 25. Electrophoresis
  26. 26. 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]
  27. 27. 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