Stability of a pharmaceutical product may be defined as the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, toxicological, protective, and informational specifications. Because suspensions are thermodynamically unstable system, physical stability of suspensions becomes as important as the chemical and biological stability.
Physical stability of suspensions is the condition in which the particles do not aggregate and in which they remain uniformly distributed throughout the dispersion. Because this ideal situation is seldom realized, it is appropriate to add that if the particles do settle, they should be easily resuspended by a moderate amount of agitation.
The formulation factors that can be adjusted to affect the physical stability of the pharmaceutical suspension are
1. Flocculation/ deflocculation
2. Sedimentation rate
When a pharmaceutical suspension is left undisturbed for a long period of time the suspended particles aggregates, sediments, and eventually cakes. For a deflocculated suspension, the particles settle at a very slow rate as small individual particles which result in a low-volume, high-density sediment that may be difficult or impossible to redisperse.
When the particles are held together in a loose open structure, as in the case of a flocculated suspension, the particles will settle rapidly and form a large-volume, low-density sediment that is readily dispersible.
The stability of either a flocculated or a deflocculated suspension can be maintained by
a. Adding charged surface-active polymer or surfactant
b. Adding oppositely charged flocculation agent
c. Adding nonionic surface-active polymer or surfactant
d. Adjusting ionic strength of vehicle
e. Adjusting pH to modify surface charge if the drug has a pKa
Thermodynamically, a disperse system may be considered to be stable whenever there is no interaction between particles. The sedimentation rate of particles in a suspension according to Stoke’s law is a function of the particle size, density of the particles, density of the vehicle, and viscosity of the vehicle.
As the particles of suspension sediment at the bottom of the container under the influence of gravity, the larger particles reach the bottom first followed by the smaller particles which occupy the space between the larger particles.
The sedimentation rate of a suspension can be controlled by
a. Increasing the viscosity of the vehicle
b. Decreasing the particle size of the drug which is best achieved by dry milling; though wet milling may be desirable for potentially explosive ingredients
c. Developing a structured vehicle which does not settle