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Kausar Ahmad Kulliyyah of Pharmacy, IIUM http://staff.iium.edu.my/akausar. Diffusion …. Contents. Introduction. The Process of Diffusion. Passive Diffusion of Ions or Molecules. Rate of Diffusion. Example. - PowerPoint PPT Presentation



Diffusion .Kausar AhmadKulliyyah of Pharmacy, IIUMhttp://staff.iium.edu.my/akausar

11Contents22Introduction33The Process of Diffusion44Passive Diffusion of Ions or Molecules

55The dashed line is a membrane that is permeable to the molecules/ions (red dots). Initially all red dots within membrane.As time passes, there is net diffusion of the red dots out of the membrane, following their concentration gradient. When the concentration of red dots is the same inside and outside of the membrane the net diffusion ceases.However, the red dots still diffuse into and out of the membrane, but the rates of the inward and outward diffusion are the same resulting in a net diffusion of zero

Rate of Diffusion66Example

Atmospheric gases mix so well that the 80 km of air closest to Earth has a uniform compositionMuch 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

7Atmospheric gases mix so well that the 80 km of air closest to Earth has a uniform compositionMuch 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.

Example: Pulmonary gas exchange

88Oxygen in the lungs first diffuses through the alveolar wall and dissolves in the fluid phase of blood. The amount of oxygen dissolved in the fluid phase is governed by Henry's Law. Oxygen dissolved in the blood may diffuse into red blood cells and bind to haemoglobin. Binding of oxygen to haemoglobin allows a greater amount of oxygen to be transported in the blood. Although carbon dioxide and oxygen are the most important molecules exchanged, other gases are also transported between the alveoli and blood. The amount of a gas that is exchanged depends on the water solubility of the gas and the affinity of the gas for haemoglobin (we will cover this in Complexation). Water vapour is also excreted through the lungs, due to humidification of inspired air by the lung tissues.Red blood cells transit the alveolar capillaries in about 3/4 of a second.Most gases (including carbon dioxide and nitrous oxide) reach equilibrium with the blood before the red blood cells leave the alveolar capillaries. Gases that reach equilibrium before the blood leaves the alveolar capillaries are perfusion limited, since the amount of the gas exchanged depends solely on the volumetric flow rate of blood past the alveoli. However, carbon monoxide is stored in such high concentrations in the blood, due to its strong binding to haemoglobin (refer to lecture on Complexation), that equilibrium is not reached before the blood leaves the alveolar capillary. Thus, the concentration of carbon monoxide in the arterial system can be used to assess the resistance of the alveolar walls to gas diffusion. Transport of carbon monoxide is thus termed diffusion limited. Oxygen is normally perfusion limited, but in disease conditions it can be diffusion limited.Diffusion in Polymers99Diffusion of a particle may also a result of movement of the polymer chain.

Occurs by threading of a molecule along its length - a process called reptation by analogy with the mechanism that a snake uses to move along the ground. In the polymer, a defect such as a kink in the chain can move at random along the chain, thereby driving the molecule through the material.

Permeation through PolymersPermeant molecule migrates through the voids between the polymer chains.Rate of diffusion depends on the size of the permeant relative to the gaps between the polymer molecules. 1010Effect of polymer crystallinitySize effect is strongest for crystalline polymers, where the material has a rigid structure.

In elastomers, movement of the

polymer molecules can allow free

passage of the permeating species,

giving higher diffusion rates which are less dependent on permeant size.1111Diffusion in liquids12End Lecture 1/312Energy is obtained from collisions between molecules, hence only a proportion of molecules with sufficiently high speed to possess enough kinetic energy can supply sufficient energy to give a molecule its activation energy.

Mean free path is the mean distance a molecule travels before it collides with another molecule..

Ref: Cambridge ThesaurusFicks First Law of DiffusionAmount 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)1313Constant is D, = diffusion coefficient (diffusivity) Diffusion rate -> dm/dt= -DA(dc/dx)

D is not constant, varies slightly with concentrationD can be considered as mean value for concentration range covered-ve because it is in the direction of decreasing concentration

1414Ficks Second Law of DiffusionThe 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)

1515Einsteins Law of DiffusionFor diffusion of colloidal particles,D = kT/ff= friction coefficientk = Boltzmann constant (1.38 x 10-23 JK-1)T = absolute temperature (K)1616Stokes LawFor spherical particles, friction coefficient is:f = 6r

= viscosity of mediumr = radius of particle

1717Stoke-Einstein LawBoltzmann constant, k = R/NR = gas constant (8.314 JK-1mol-1)N = Avogadro number (6.022 x 1023 mol-1)

From Einstein:D = kT/fD = kT/ 6rD = RT/6Nr

1818Measurement of DiffusionPorous disc methodm = -DA(c1 c2)(t1 t2)/Lm = amount of solute diffusedc1,c2 = solute concentration at either side of the disc at time t1,t2A = cross section of poresL= effective length of poresA/L is obtained by calibrating the cell in solute with known D

1919Solution: t1, c1Path of a particle diffusing through porous discSolvent: t2, c2


2020Limitation of Porous disc method2121dm/dt = - D. A. dc/dx

Small solutes travel very much faster than big solutes.When small solutes travel through the porous disc:They go through the pores without much difficulty.The time taken to travel the distance L depends on the size of the small solutes. This becomes the defining factor for dx.Thus, dx is indicated as a relatively low figure.

For the determination of high molecular weight solutes:The solutes may not even enter the pores due to size of pores smaller than size of solutes. Even if they manage to pass through the pores, they will move very slowly because of the size. Since dx has been determined by calibration using low molecular weight solute, and has a low value, the diffusion coefficient, D, of the high molecular weight solute would be on the low side, and is thus misleading..

Diffusion through gels

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

22Solution: M0


xx2t22Continue Diffusion through gels

ApplicationsCup plate method of assay of antibioticsDiffusion through agar gels seeded with test organismZone of growth inhibition proportional to antibiotic potency2323Continue Diffusion through gels

Zone of growth inhibition proportional to antibiotic potency24inhibition of growth zonefilled with antibiotic

24Membrane Functions2525Membrane allows separation of small molecules from big macromolecules2626

Passive Diffusion2727

Facilitated Diffusion2828Facilitated Diffusion This animation illustrates protein mediated, facilitated diffusion out of a cell.

2929The protein is a uniporter, transporting one substrate across the membrane. In facilitated diffusion, the protein allows molecules or ions to enter or leave the cell moving DOWN their concentration gradient.The concentration of molecules or ions (illustrated by the red dots) is greater inside the cell than outside the cell. Thus, the protein carrier allows the red dots to leave, down their concentration gradient. If the concentration of red dots was higher outside of the cell than inside of the cell the protein would allow the dots to pass into the cell just as easily. When does a cell let materials diffuse out using a facilitated diffusion system? An example of this situation is found in the liver cells which control the concentration of glucose in the blood. Liver cells store excess glucose as glycogen when blood sugar levels are high (just after a high carbohydrate meal) and then breakdown the glycogen as glucose-1-phosphate which is converted to glucose-6-phosphate which is finally converted to free glucose. The breakdown of glycogen is closely controlled by hormones. The glucose-1-P and the glucose-6-P produced by glycogen breakdown are impermeable to the membrane. However, there is a transport protein which functions by facilitated diffusion which allows glucose to freely pass back and forth across the membrane.

Example: Diffusion across GITAbsorption of weakly acidic/basic drugs Passive diffusion of un-ionised molecule across lipoidal membrane of GIT.3030Example: Purification by dialysis

3131Diffusion through membrane32Water renewed to establish concentration gradient Semi-permeable membrane

Small moleculesBig molecule32Example: Diffusion from Dosage Form

3333Rate 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, tD = diffusion coefficiente = porosity of matrixCs = solubility of drugA = concen


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