Disperse System

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PR 1102 Physical Pharmacy

Kang [email protected]

Disperse System


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Disperse System

Dispersed phase

Continuous phase

Interface


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Disperse System

Disperse systems consist of particulate matter(dispersed phase) distributed throughout acontinuous medium

Dispersed material ranges in size, from moleculardimensions to particles of millimeters

Many biological drugs that have been discovered aremacromolecules that exist in colloidal systems (e.g.

proteins and DNA). Nanoparticulate systems are also emerging for

improved drug delivery.


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Classification by State

a Continuous phase

Gas Liquid Solid

D i s p e r s e

d p

h a s e

Gas Nil Foam Solid foam

Liquid Liquid aerosol Emulsion Gel

Solid Sold aerosol Suspension Solid sol
http://www.naturalhealthlibrarian.com/images/asprin.gifhttp://nickobeano.files.wordpress.com/2008/01/cheese_oh_cheese.jpghttp://www.universalws.com/images/topcare%20calamine%20lotion%20(Small).JPGhttp://www.medgadget.com/archives/img/Exubera.jpghttp://www.dollychar.com/blog/wp-content/uploads/2009/01/dettol-173x300.jpghttp://www.firstpr.com.au/show-and-tell/green-ants/DSC00286-beach-foam-rainbow-colours-trippier.jpg


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Dispersion Stability


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Brownian Motion

Spontaneous, irregular zig-zag movement ofparticles because of random collisions withmolecules .

t -time D-diffusion coefficient; r-averagedisplacement


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Reynolds Number

Re vr r is the radius of a sphere v is the velocity of the sphere is the density of the liquid is the viscosity of the liquid Reynolds number measures the relative

importance of inertia and viscosity For particles on a colloidal scale, Re is small
http://en.wikipedia.org/wiki/File:Stokes_sphere.svg


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Stokess Law

6d F rv r is the radius of a sphere v is the velocity of the sphere is the viscosity of the liquid F d is the drag force Stokes law is derived from the Navier Stokes

equations for small Reynolds numbers.


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Einsteins Relation

k B is the Boltzmanns constant D is the diffusion coefficient T is the temperature k drag is the drag coefficient

B

drag

k T D k


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Stokes-Einstein Equation

If we know the diffusion coefficient D, thenthe size of the particle can be estimated bythe Stokes-Einstein equation .

B

drag

k T D

k

6d drag F rv k v

6 Bk T D

r


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Rate of Sedimentation

To calculate v when the gravitational anddrag forces are balanced

Smaller particles and higher viscosities give

smaller sedimentation rate

3 3 34 4 4

3 3 3 g solid Liquid F r g r g r g

3463

rv r g

6d F rv

22

9

r g v


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One Example: Suppositories

Suppository bases include cocoa butter,glycerinated gelatin, hydrogenated vegetableoils, polyethylene glycols

Cocoa butter melt to incorporate fine particlesand then cool in molds. It is a colloid-coarsedisperse system and particles may sediment

Copper sulphate suppository preparationprocess: Grind coarse powders, melt base andincorporate the find powders
http://www.detronizator.org/wp-content/uploads/2007/09/buttercocoadeo.jpg


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Interactions Between Particles

Inter-particle forces DLVO theory Zeta potential

Dispersed phase interactions


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DLVO Theory Deryagin-Landau and Verwey-Overbeck The stability of a particle in solution depends on

its total potential energy function


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Van der Waals Attractive Forces

212 A A

V d A is a constant and d is the particle separation

distance. If a repulsion mechanism does not

exist then flocculation will eventually takeplace.


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Electrostatic Repulsive Forces V R2

2 kd

RV r e

r is the particle radius, k is a function of theionic composition and is the zeta potential


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Colloid Stability Mechanism


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To Increase Repulsive Forces V R Steric repulsion - this involves polymers added

to the system adsorbing onto the particlesurface and preventing the particle surfaces

coming into close contact and at thoseseparations the van der Waals forces are tooweak to cause the particles to adhere

Electrostatic or charge stabilization - this is theeffect on particle interaction due to thedistribution of charged species in the system


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Charged Particle and Zeta Potential

Stern layer

Negatively charged particle


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Diffuse Layer

Diffuse layer


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Slipping Plane

Hydrodynamic planeof shear (slippingplane)


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Zeta Potential

The zeta potential is the electrical potential atthe hydrodynamic plane of shear

It depends not only on the particle surface but

also on the dispersant It can be affected by small changes in the pH

or ionic strength of the medium Particles interact according the magnitude of

the zeta potential, not their surface charge Therefore, it can be used to predict stability


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Significance of Zeta Potential

If all the particles have a large negative orpositive zeta potential they will repel eachother and there is dispersion stability

If the particles have low zeta potential valuesthen there is no force to prevent particlescoming together and there is dispersion

instability The dividing line of stable and instable zeta

potential is +30 mV or -30mV


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Factors Affecting Zeta Potential

Changes in the pH of the sample The conductivity of the medium

(concentration and type of salt)


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pH Effects on Bovine Serum Albumin(BSA) Zeta Potential

Stable

Stable

Unstable

Z e t a P o t e n t i a

l ( m

V )

pH

The rule of thumb of stability +/- 30 mV.


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Conductivity Effects on BSA Zeta Potential


l ( m V

)

Concentration (Log(mol/l)


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An Example of Liposome

Plasmids Cationic liposome

Plasmid - cationic liposome complex


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Liposome Complex Zeta-potential

Molar ratio of Plasmid and liposome


l ( m V

)

P a r t i c

l e d i a m

e t e r ( n m

)


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PEG-coated Liposome

PEG Liposome complex

Liposome Polyethylene glycol (PEG)


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l ( m V

)

Ratio of PEG2000

PEG-coated Liposome Zeta-potential


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If an electric field is applied across a sample,charged particles suspended in the mdeiumare attracted towards the electrode ofopposite charge

The particles move with a velocity dependson: (i)Field strength, (ii) dielectric constant ofmedium and (iii) viscosity of the medium and(iv) zeta potential.

Parameters (i)-(iii) are know, so zeta potentialcan be determined

Measure Zeta-potential

Disperse System

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