Diffusion ….

1. Kausar Ahmad Kulliyyah of Pharmacy, IIUM http://staff.iium.edu.my/akausar Diffusion ….

2. Contents

3. Introduction

4. The Process of Diffusion

5. Passive Diffusion of Ions or Molecules

6. Rate of Diffusion

7. Example • Atmospheric gases mix so well that the 80 km of air closest to Earth has a uniform composition • Much less mixing occurs in the oceans, and the differences in composition at various depths support different species. • Rocky solids intermingle so little that adjacent strata remain separated for millions of years. Al-Quran 35:27

8. Example: Pulmonary gas exchange

9. Diffusion in Polymers

10. Permeation through Polymers • Permeant molecule migrates through the voidsbetween the polymer chains. • Rate of diffusion depends on the size of the permeantrelative to the gapsbetween the polymer molecules.

11. Effect of polymer crystallinity • Size effect is strongest for crystallinepolymers, where the material has a rigid structure. • In elastomers,movement of thepolymer molecules can allow free • passage of the permeating species, • giving higher diffusion rateswhich are less dependent on permeant size.

12. Diffusion in liquids End Lecture 1/3

13. Fick’s First Law of Diffusion Amount of substance, dm, diffusing in x direction, in time dt, across an area A, Is proportional to concentration gradient dc/dx. Thus, the diffusion rate is: dm/dt = constant(A)(dc/dx)

14. Constant is D, = diffusion coefficient (diffusivity) Diffusion rate -> dm/dt= -DA(dc/dx) • ‘D’ is not constant, varies slightly with concentration • ‘D’ can be considered as mean value for concentration range covered • “-ve” because it is in the direction of decreasing concentration

15. Fick’s Second Law of Diffusion The concentration rate of change, within diffusional field, at a particular point, is proportional to rate of change in concentration gradient. Dc/dt = D(d2c/dx2)

16. Einstein’s Law of Diffusion For diffusion of colloidal particles, D = kT/f f= friction coefficient k = Boltzmann constant (1.38 x 10-23 JK-1) T = absolute temperature (K)

17. Stoke’s Law For spherical particles, friction coefficient is: f = 6r  = viscosity of medium r = radius of particle

18. Stoke-Einstein Law Boltzmann constant, k = R/N R = gas constant (8.314 JK-1mol-1) N = Avogadro number (6.022 x 1023 mol-1) From Einstein: D = kT/f • D = kT/ 6r • D = RT/6Nr

19. Measurement of Diffusion Porous disc method m = -DA(c1 – c2)(t1 – t2)/L • m = amount of solute diffused • c1,c2 = solute concentration at either side of the disc at time t1,t2 • A = cross section of pores • L= effective length of pores • A/L is obtained by calibrating the cell in solute with known D

20. Solution: t1, c1 A Solvent: t2, c2 Path of a particle diffusing through porous disc

21. Limitation of Porous disc method

22. Diffusion through gels x Solution: M0 Gel Mt = Moe(-x2/4Dt) ln Mt = ln Mo + (-x2/4Dt) ln Mt = ln Mo - (x2/4Dt) x2/4Dt = ln Mo - ln Mt • x2/t = 2.303 x 4D(log Mo - log Mt) • A plot of x2 against t gives a straight line, • Slope: 2.303 x 4D(log Mo - log Mt) • D can be calculated x2 t

23. Continue Diffusion through gels Applications Cup plate method of assay of antibiotics • Diffusion through agar gels seeded with test organism • Zone of growth inhibition proportional to antibiotic potency

24. Continue Diffusion through gels • Zone of growth inhibition proportional to antibiotic potency inhibition of growth zone filled with antibiotic

25. Membrane Functions

26. Membrane allows separation of small molecules from big macromolecules

27. Passive Diffusion

28. Facilitated Diffusion

29. Facilitated Diffusion • This animation illustrates protein mediated, facilitated diffusion out of a cell.

30. Example: Diffusion across GIT Absorption of weakly acidic/basic drugs • Passive diffusion of un-ionised molecule across lipoidal membrane of GIT.

31. Example: Purification by dialysis

32. Diffusion through membrane Semi-permeable membrane Small molecules Water renewed to establish concentration gradient Big molecule

33. Example: Diffusion from Dosage Form

34. Rate of drug released from one surface of insoluble matrix (Higuchi,1963):Q = DeCs(2A – eCs)t/t)1/2 Q= amount of drug released per unit area at time, t D = diffusion coefficient e = porosity of matrix Cs = solubility of drug A = concentration/amount of drug in the tablet  = tortuosity of matrix End Lecture 2 /3

35. Factors affecting DiffusionFick’s First Law:dm/dt= -DA(dc/dx),Stoke-Einstein Law:D = RT/6Nr

36. Continue Factors affecting Diffusion

37. Continue Factors affecting Diffusion

38. Continue Factors affecting Diffusion

39. Example of a membrane: Gelatin

40. Application of Diffusion

41. Continue Application of Diffusion

42. Continue Application of Diffusion

43. Continue Application of Diffusion

44. Continue Application of Diffusion

45. Example in research: Lateral Diffusion of Proteins Source: http://bio.winona.msus.edu/berg/ANIMTNS/difusean.htm

46. Example in research:Diffusion of Membrane Proteins Source: http://bio.winona.msus.edu/berg/ANIMTNS/Prot-dif.htm

47. References Rawlins, E. A. (1984). Bentley’s Textbook of Pharmaceutics 8th Ed. BailliereTindall. Chapter 8 http://bio.winona.msus.edu/berg/ANIMTNS/Prot-dif.htm http://cr.middlebury.edu/biology/labbook/diffusion// http://www.d.umn.edu/~sdowning/Membranes/lecturenotes.html http://www.biologycorner.com/bio1/diffusion.html# Thank you to contributors for images used in this presentation.