A Pharmaceutical suspension is a coarse dispersion in which internal phase (therapeutically active ingredient)is dispersed uniformly throughout the external phase. The internal phase consisting of insoluble solid particles having a range of size(0.5 to 5 microns) which is maintained uniformly through out the suspending vehicle with aid of single or combination of suspending agent. The external phase (suspending medium) is generally aqueous in some instance, may be an organic or oily liquid for non oral use.
INTERFACIAL PROPERTIES OF SUSPENDED PARTICLES :
- Work must be done to reduce a solid to small particles and disperse them in a continuous medium.
- The large surface area of the particles that results from the comminution is associated with a surface free energy that makes the system thermodynamically unstable, by which we mean that the particles are highly energetic and tend to regroup in such a way as to decrease the total area and reduce the surface free energy.
- The particles in a liquid suspension therefore tend to flocculate, that is, to form light, fluffy conglomerates that are held together by weak van der Waals forces.
- Under certain conditions—in a compacted cake, for example—the particles may adhere by stronger forces to form what are termed aggregates.
- Caking often occurs by the growth and fusing together of crystals in the precipitates to produce a solid aggregate.
- The formation of any type of agglomerate, either floccules or aggregates, is taken as a measure of the system’s tendency to reach a more thermodynamically stable state.
- An increase in the work, W, or surface free energy, ΔG, brought about by dividing the solid into smaller particles and consequently increasing the total surface area, ΔA, is given by ΔG = γSL . ΔA.
where γSL is the interfacial tension between the liquid medium and the solid particles.
- To approach a stable state, the system tends to reduce the surface free energy; equilibrium is reached when ΔG = 0. This condition can be accomplished, as seen from equation .
- By a reduction of interfacial tension, or it can be approached by a decrease of the interfacial area.
- The latter possibility, leading to flocculation or aggregation, can be desirable or undesirable in a pharmaceutical suspension.
- The interfacial tension can be reduced by the addition of a surfactant but cannot ordinarily be made equal to zero.
- A suspension of insoluble particles, then, usually possesses a finite positive interfacial tension, and the particles tend to flocculate.
- The forces at the surface of a particle affect the degree of flocculation and agglomeration in a suspension.
- Forces of attraction are of the London–van der Waals type; the repulsive forces arise from the interaction of the electric double layers surrounding each particle.
- The formation of the electric double layer deals with interfacial phenomena.
- The potential energy of two particles is plotted as a function of the distance of separation.
- When the repulsion energy is high, the potential barrier is also high, and collision of the particles is opposed.
- The system remains deflocculated.
- When sedimentation is complete, the particles form a close-packed arrangement with the smaller particles filling the voids between the larger ones.
- Those particles lowest in the sediment are gradually pressed together by the weight of the ones above; the energy barrier is thus overcome, allowing the particles to come into close contact with each other.
- To resuspend and redisperse these particles, it is again necessary to overcome the high-energy barrier.
- Because this is not easily achieved by agitation, the particles tend to remain strongly attracted to each other and form a hard cake.
- When the particles are flocculated, the energy barrier is still too large to be surmounted, and so the approaching particle resides in the second energy minimum, which is at a distance of separation of perhaps 1000 to 2000 Å.
- This distance is sufficient to form the loosely structural flocs.
- These concepts evolve from (DLVO) theory for the stability of lyophobic sols.
- To summarize, flocculated particles are weakly bonded, settle rapidly, do not form a cake, and are easily resuspended.
- Deflocculated particles settle slowly and eventually form a sediment in which aggregation occurs with the resultant formation of a hard cake that is difficult to resuspend.
Multiple choice questions (MCQs)
1.Pharmaceutical suspension are generally
2.Rate of sedimentation is high in
3.Cake formation is characteristic feature of
4.For ideal suspension, the sedimentation volume should be
b)Equal to one
c)Less than one
d)More than one
5.If particle size is 1-100µm then
6.In dilute suspension the concentration of solid should be
7.The bioavailability of flocculated suspension is
c)Both a and b
d)None of the above
8.In suspension, if particle size of suspended particle decrease so
a)Surface free energy decrease
b)Surface area decrease
c)Surface free energy increase
d)System becomes thermodynamically stable
9.As per sedimentation theory, if particle size of suspended particle decrease so sedimentation rate decrease. So what would be the effect on absorption of drug when taken orally?
d)Both a and b
10.The sedimentation volume have a range from
11.A suspension is formed from uniform particles of solid, of diameter 10 Mm, suspended in a solvent. What is the best description of this system?
a)Monodisperse and coarse
b)Monodisperse and colloidal
c)Polydisperse and coarse
d)Polydisperse and colloidal
12.Which one of the following dispersions does not have liquid continuous phase?
13.Following is not a mechanism for the separation of a physically unstable suspension of magnesium hydroxide in water?
14.Brownian movement of particle in suspension cause
d)Increase sedimentation rate
15.Suspended particles become flocculated in a suspension, because
a)Particles are closely packed
b)Attractive forces between particles are appreciable
c)Repulsive forces between particles are appreciable
d)Vehicle rejects the particles
- b)De flocculated
- c)Less than one
- b)Comparatively less
- c)Surface free energy increase
- a)Absorption increase
- a)Monodisperse and coarse
- c)Prevent sedimentation
- b)Attractive forces between particles are appreciable
1. GAURAV KUMAR JAIN – THEORY & PRACTICE OF PHYSICAL PHARMACY, 1st edition 2012 Elsevier, page no. 204-206.
2. Martins Physical Pharmacy, 6th edition 2011, page no. 747-750.