norita - pharmaceutical engineering 5 - assignment 4

7/30/2019 Norita - Pharmaceutical Engineering 5 - Assignment 4

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Norita

Pharmaceutical Engineering 5

1. Explain the theory and sedimentation behavior of flocculated and deflocculatedsuspension and the relevance with pharmaceutical suspension dosage form.

Theory of Fluccolated and Deflocculated SuspensionFlocculation is the formation of light, fluffy groups of particles held together by Van

Der Waals forces. The basic concern in developing a suitable suspension is to adequately

control the rate of settling and ease of redispersion, as well as, the prevention of caking

the particles as a dense mass at the bottom of the container. The best approach is to

achieve a controlled flocculation of the particles, where they appear as floccules or like

tufts of wool with a loose fibrous structure. These particles settle rapidly, forming a

loose adhering system with a large sediment height.

Deflocculation is the absence of association which occurs when repulsive forces

between particles predominate. If repulsion forces prevail, the particles separate or

deflocculate. Particles in these systems settle very slowly in stages, but ultimately form a

dense sediment which is considerably more compact than the corresponding sediment

of a flocculated system and more difficult to resuspend. Particle motion in the

suspension is due to Brownian motion, convection currents, and sedimentation. When

the particles settle, a dense mass is formed since there is no association between

deflocculated particles. Downward movement due to gravity and the lateral motion due

to Brownian movement facilitates tight packing of larger particles with the smaller

particles filling the void spaces. Particles at the bottom of the cake are gradually pressed

together by the weight of the ones above. In order to stabilize deflocculated systems, it

is necessary to add a suspending and gelling agent to retard settling and agglomeration

of the particles by functioning as an energy barrier.

Sedimentation Behavior of Flocculated and Deflocculated SuspensionFlocculated Suspensions

In flocculated suspension, loose aggregates will cause increase in sedimentation rate

due to increase in size of sedimenting particles. Hence, flocculated suspensions

sediment more rapidly. Here, the sedimentation depends not only on the size of the

flocs but also on the porosity of flocs. In flocculated suspension the loose structure of

the rapidly sedimenting flocs tends to preserve in the sediment, which contains an

appreciable amount of entrapped liquid. The volume of final sediment is thus relatively

large and is easily redispersed by agitation.


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Deflocculated suspensions

In deflocculated suspension, individual particles are settling, so rate of sedimentation is

slow which prevents entrapping of liquid medium which makes it difficult to redisperse

by agitation which called cracking. In deflocculated suspension larger particles settle fast

and smaller remain in supernatant liquid so supernatant appears cloudy whereby in

flocculated suspension, even the smallest particles are involved in flocs, so the

supernatant does not appear cloudy.

Comparative Properties of Flocculated and Deflocculated SuspensionFlocculated Suspension Deflocculated Suspension

Particles form loose aggregatesParticle exist in a suspension as separate

entities

Rate of sedimentation is high, so it formed

rapidly

Rate of sedimentation is slow, so it formed

slowly

The sediment eventually becomes very

loosely packed and easy to disperse, so as

to reform the original suspension

The sediment eventually becomes very

closely packed and hard cake is reformed

so hard to redisperse

The suspension is somewhat unslightly,

due to rapid sedimentation and the

presence of an obvious, clear supernatant

region.

The suspension has a pleasing appearance

because uniform dispersion of particles

2. Advantage and disadvantage of flocculated and deflocculated system in pharmaceuticalpreparation.

Flocculation

Advantages Disadvantages

Flocculation removes contaminants andloose, airborne particles from water or

other solutions.

It is very simple and is produced whenflocculants are added to a solution and the

particles bond together.

Flocculation can be done in a lab or in the

Flocculation only occurs in liquids andcannot be used on metals or other

substances.

Not all flocculants can be used with thesame solutions or under the same

conditions.

The suspension is somewhat unslightly,


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field and takes minutes or hours, depending

on the quantity of the solution.

It can also be stopped or prevented byadding deflocculants to a solution.

Rate of sedimentation is high, therefore itform rapidly.

due to rapid sedimentation and the

presence of an obvious, clear supernatant

region. This can be minimized if the

volume of sediment is made large. Ideally,

volume of sediment should encompass

the volume of the suspension.

Deflocculation

Advantages Disadvantages

T he suspension has a pleasing appearance,since the suspended material remains

suspended for a relatively long time.

Particles settle independently andseparately.

Rate of sedimentation is slow, as the sizesof particles are small.

The sediment eventually becomesvery closely packed, due to weight of

upper layers of sedimenting material.

Repulsive forces between particles are

overcome and a hard cake is formed

which isdifficult, if not impossible, to

redisperse.

3. Explain the electrolytes and zeta potential related with the stability of suspension system.Zeta Potential

The zeta potential is defined as the difference in potential between the surface of the tightly

bound layer (shear plane) and electro-neutral region of the solution. The potential drops off

rapidly at first, followed by more gradual decrease as the distance from the surface

increases. This is because the counter ions close to the surface acts as a screen that reduce

the electrostatic attraction between the charged surface and those counter ions further

away from the surface.

Zeta potential has practical application in stability of systems containing dispersed particles

since this potential, rather than the Nernst potential, governs the degree of repulsion

between the adjacent, similarly charged, dispersed particles. If the zeta potential is reduced

below a certain value (which depends on the particular system being used), the attractive

forces exceed the repulsive forces, and the particles come together, which called


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flocculation. Deflocculation of particles is obtained when the zeta potential is higher than

the critical value and the repulsive forces supersede the attractive forces.

Electrolytes

Electrolytes act by reducing the zeta potential, which brings the particles together to form

loosely arranged structures. The flocculating power increases with the valency of the ions.

Hence, calcium ions are more powerful than sodium or potassium ions. However, trivalent

ions are less commonly used because of their toxicity. When electrolytes are added to a

positively charged deflocculated suspension, zeta potential decreases slowly. At certain

stage, upon persistent addition, it becomes zero. Beyond that limit, zeta potential becomes

negative. As zeta potential decreases, the sedimentation volume increases sharply up to a

point. The sedimentation volume reaches its maximum value and remains relatively

constant within a certain range of zeta potential, where it changes from low positive

potential to low negative potential. When the potential becomes too negative, the

sedimentation volume decreases again. An experiment by microscopic examination showed

that flocculation increases with the addition electrolytes, and the extent of flocculation

coincided with the sedimentation volume. Caking was observed at less than the maximum

values of sedimentation volume.

4. Why multiple emulsion system which is water in oil in water and oil in water in oil is used?Multiple emulsions are complex systems in which the drops of the dispersed phase contain

smaller droplets that have the same composition as the external phase. Normally consist of

a liquid that is miscible, and in most cases identical, with the continuous phase.The most

promising use of multiple emulsions is in the area sustained release, drug formulation since

the oil layer between the two aqueous phases can behave like a membrane controlling

solute release. The main reason why multiple emulsion was used is to deliver the API

achieve the target of releasing. Other reason of multiple emulsions were used because the

system was:

Remarkable degree of biocompatibility Complete biodegradability Hydrophilic as well as hydrophobic drug can be entrapped Protection from the inactivation by the endogenous factors Increase in drug dosing intervals Taste masking of bitter drugs


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Water in oil in water (W/O/W)

Water-in-oil-in-water (W/O/W) multiple emulsions are emulsion systems where small water

droplets are entrapped within larger oil droplets that in turn are dispersed in a continuous

water phase. Because of the presence of a reservoir phase inside droplets of another phase

that can be used to prolong release of active ingredients. W/O/W emulsion possess many of

the advantages of W/O emulsion, but in addition have a low viscosity due to the lower

viscosity of the aqueous external phase, which makes them more convenient and useful

especially to inject/ W/O/W multiple emulsions may be prepared with two step procedures.

W/O/W emulsions able to break and release their inner aqueous phase under shear rate are

which compatible with cosmetic applications.

A unique property of W/O/W multiple emulsions compared to simple W/O emulsions is the

diffusion of water through the oil phase because of unbalanced osmotic pressures between

the internal and external aqueous phases. The oil layer acts as a membrane separating these

2 aqueous phases. Polar molecules dissolved in either the internal aqueous phase or the

external continuous aqueous phase can pass through the oil layer by diffusion because of

the concentration gradient. In the case of water this is driven by osmotic pressure.

Oil in water in oil (O/W/O)

In O/W/O systems an aqueous phase (hydrophilic) separates internal and externaloil phase.

In other words, O/W/O is a system in which water droplets may besurrounded in oil phase,

which in true encloses one or more oil droplets. Liquid membrane emulsions of the o/w/o

type have been used to separate hydrocarbons where the aqueous phase serves as the

membrane and a solvent as the external phase.

norita - pharmaceutical engineering 5 - assignment 4

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