Pharmaceutical Suspensions: Formulation, Properties, and Stability, Cheat Sheet of Pharmacy

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Suspension

• A suspension may be defined as heterogeneous (biphasic) system comprising

of a finely divided solid phase (the dispersed phase) uniformly dispersed in a

liquid phase (the continuous phase).

• A pharmaceutical suspension is a coarse dispersion in which insoluble solid

particles are dispersed in a liquid medium.

• Suspension often provides a means of supplying an insoluble and often

distasteful substance in a form that is pleasant to taste.

• Chloramphenicol is very bitter and cannot be given in a liquid form to children.
• Chloramphenicol palmitate, an insoluble salt, can be formulated as a

suspension suitable for pediatric use.

Criteria for good

suspension

A suspension should have following properties:

• Suspended matter should not settle rapidly.
• The particles which settle should not form a hard

cake and should re-disperse easily on shaking.

• A good suspension should not be too viscous to

pour.

• In case of parenteral preparations , the suspension

should flow out of syringe needle.

• Suspension for external application should be easy

to apply and not run off. Also, it should not dry off

too quickly.

•A good suspension should have smooth, elegant appearance.

•It must have an acceptable color and odor.

•It must b resistant to microbial attack.

•The suspended ingredients should not hydrolyze or degrade too rapidly or undergo changes in polymorphic form.

•Ideally suspension be thixotropic i.e., these should become viscous on standing and should thin readily on shaking.

•This prevent sedimentation of drug during storage and allow its easy withdraw on shaking.

1. Surface Free Energy

• During formulation of suspension, work

is done to reduce the particle size or to

disperse in a continuous medium.

• This makes system thermodynamically

unstable. In order to increase the

stability, particles either flocculate, i.e.,

form a light, fluffy conglomerate that are

held together by weak van der waal‟s

forces or they settle down to form a

compact aggregate.

• Cracking usually occur by the growth and fusing

together of crystals in the precipitate.

• The increase in free energy due to reduction of particle

size by the equation:

∆G=γSL ∆A

• Where „g‟ is the increase in work or surface free energy.
• ′γSL′ is the interfacial tension between liquid medium

and solid particles

• „A‟ is the total surface area.

• The interfacial tension can be reduced by the addition of

wetting agent which gets adsorbed on the surface of

suspending particles.

• The wetting agent, however, is not able to reduce the

interfacial tension to zero and hence a suspension

generally possesses a finite positive interfacial tension as

a result of which the suspended particle tends to flocculate

or aggregate.

• The forces acting on the surface of suspended particles also

affect the degree of flocculation in a suspension.

• Forces of attraction arise from “van der waal‟s” forces

while forces of repulsion result from interaction of electric

double layer surrounding each particle.

• These result in the potential energy of attraction and

potential energy of repulsion.

• As a result, they experience attractive forces and ultimately from a

hard cake like sediment.

• To regain original energy barrier, a high energy barrier is required.

Hence, even on vigorous agitation, the re-dispersion of particles is not

easily achieved and the particles remain as a cake.

• When the particles are flocculated, the energy barrier is still too large

to be overcome and therefore the particles remain separate by a

distance from 100 to 2000a in the secondary minimum.

• The distance is sufficient to form the loosely structured floccules.

Potential energy curve for particle

interactions in suspensions

• In a deflocculated suspension, the larger particles settle relatively at

a faster rate than the smaller particles.

• As a result a clear boundary between the sediment and the

dispersion medium cannot be easily distinguished and the supernatant

liquid remains cloudy for a considerable period of time.

• However, in case of flocculated suspension, groups of particles are

aggregated into flocs and the flocs tend to fall together while setting

resulting in a clear boundary between the sediment and the

supernatant liquid.

Sedimentation

parameter

• Sedimentation volume
• Degree of flocculation

• For example, if the sedimentation volume is 0.70 it means 70% of the total

volume of the suspension is occupied by the sediment.

• When F=1 , the sediment volume and the total volume are equal and such a

suspension does not show any clear supernatant liquid on standing.

• Such a suspension looks elegant and is pharmaceutically acceptable.
• It is also possible for the sedimentation volume to exceed the total volume of

the suspension i.e., for F to become greater than 1.

• It indicates that the network of flocs formed in the suspension is loose and

fluffy and encompasses a volume greater than the original volume of the

suspension.

Degree of

flocculation

• The sedimentation volume only gives a

qualitative idea regarding the flocculation in suspensions.

• The degree of flocculation is a better parameter to compare different formulation in terms of flocculation.
• It is the ratio of the sedimentation volume of the flocculated suspension (f)

to the sedimentation volume of the suspension when deflocculated (F_∞),

β= F / F_∞