Suspension Stability Problems

The ideal characteristics of a suspension are:

        1. The sedimentation is less as possible

        2. The sediment is redispersible

According to strokes law:

The rate of sedimentation of a particle in a liquid medium is

• Directly proportional to the diameter of the particle

• Directly proportional to the density difference between particle and medium

• Inversely proportional to the viscosity of the medium.

• Mathematical expression

Where,

V= velocity of sedimentation in cm/sec

r= particle radius in cm

D= particle diameter in cm

d1=density of the particle in gm/cc

d2=density of the medium in gm/cc

g= gravitational constant =980cm/sec2

η= viscosity of the medium.

The characteristics of a suspension are that the particles of the suspension are more or less settle down on keeping for sometime. But the rate of sedimentation is different for different suspension.

Problems associated with suspension preparation

    1.  Caking and poor redispersibility

    2.  Cap locking

    3.  Color change

    4.  Crystal growth

    5.  Deflocculation

    6.  Decrease in drug potency

    7.  Change in flavor

    8.  PH change

    9.  Change in viscosity

  10.  Rapid settling

  11.  Change in particle size

  12.  Microbial growth

  13.  Foaming

  14.  Chemical interaction

  15.  Dispersion of hydrophobic drug

Caking and poor redispersibility

Caking is a compact mass of insoluble solids particle formed generally in deflocculated suspension.

Cause:

Due to the smaller size of the particle, the rate of sedimentation of deflocculated suspension is very slow. The sediment eventually comes very close packed, owing to the weight of the upper layers of the sediment materials.

Due to the particle-particle interaction, the repulsive forces between particles are overcome and a hard cake is formed which is difficult to redisperse.

Remedy:

a. By using flocculating agent: flocculating agents prevent cake formation by the flocculation of the particles. The process of flocculation as well as the stabilization of the suspension are mentioned below:

– The particles, irrespective of their charge are coated with positively charged agent.

– The particles are flocculated by the use of a negatively charged agent to bring the product in to the non caking zone.

– Finally a minimum amount of the desired suspending agent or mixture of suspending agents is added and the suspension is again observed for optimum flocculation and freedom from caking.  

Examples of flocculating agents: Electrolytes, Surfactants, polymers

b. By using viscosity imparting agent:

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Cake formation is due to the sedimentation of the particles. The greater is the viscosity of the liquid, the less is the rate of sedimentation and less is the cake formation. So we can prevent the cake formation using viscosity imparting agents.

Examples : Acacia, Tragacanth, Agar

c. Caking is prevented by controlling of pH of the dispersion phase.

d. It can be controlled by decreasing particle size.

Cap Locking

Cause

Caplocking is a filling problem which occurs when the dispersed particles crystallize on the threads of the bottle cap and interface in cap removal.

Remedy

Caplocking can be prevented by using different vehicle containing sucrose, glucose, sorbital and glycerine.

Color change:

Cause:

Light sensitive color may be changed in presence of light.

Due to the increased in surface area some color may be changed.

Remedy:

By keeping the bottle in dark place.

Crystal growth:

Cause:

There is always a degree of crystal growth which mainly occurs in storage condition due to-

• Temperature fluctuation

• pH change

• Impurity

• Low solubility

Remedy:

• By adding surfactants

• By controlling solubility

• By Controlling pH

• By preventing temperature fluctuation

Deflocculation:

Cause:

• Change in pH

• Adding of excess electrolytes.

• Due to drug degradation.

Remedy:

By using flocculating agent

– Electrolytes

– Detergents

– Polymer

Decrease in drug potency:

Cause:

– Due to decomposition of the drug.

– Due to the change in particle size

– By keeping suspension for long time.

Change in flavor:

Cause:

– Flavoring agents are volatile compounds. So the flavor of the suspension may be changed on long term use.

– Remedy:

– By using sufficient flavoring agents.

pH Change:

Causes:

• Drug degradation

• Alkalinity of glass bottle.

• Microbial growth

Remedy:

By adding buffering agents. Buffering agents help to maintain chemical stability also ensure physiological compatibility.

Change in viscosity:

The viscosity of the suspension may be changed on long term use.

Remedy:

By using sufficient viscosity imparting agents.

Rapid settling:

Some times rapid settling of particles is found in suspension.

Remedy:

– By decreasing the particle size.

– By using viscosity imparting agents.

Change in particle size:

Some times the particle size may be changed. Generally particle size is increased. Increased particle size helps in rapid settling.

Remedy:

By using viscosity imparting agents.

Microbial growth:

Most suspensions have almost neutral pH and susceptible for microbial growth.

Remedy: Preservatives should be added.

Foaming:

If the density of the particle is less than the density of the liquid medium, the negative velocity of the particle results, this is the rate of floating or creaming.

Remedy:

Minor modification to the aqueous phase is necessary.

Chemical interaction:

Chemical interaction may be arisen during the addition of additives to the drug such as cationic surfactants react with any anionic ingredients.

Remedy:

Care should be taken when additive added to the drug.

Dispersion of hydrophobic drugs:

Hydrophobic drug particles do not dissolve in water. So suspension of hydrophobic drug creates some problem in particle dispersion.

Remedy:

Wetting agents are used in this concern which promotes the dispersion of hydrophobic drug in water.

Examples of wetting agents:

– Surfactants

– Sodium carboxy methyl cellulose (Sodium-CMC).

– Bentonite ( colloidal hydrated aluminium silicate)

– Veegum (colloidal aluminium magnesium silicate.