Important Considerations in Formulation of Suspension

Formulation of a pharmaceutical suspension requires a knowledge of the properties
of both the dispersed phase and the dispersion medium. The material for the formulation
of suspensions should be carefully selected keeping in mind the route of
administration, intended application, and possible adverse effects.

The following are the most important factors to be considered during the formulation of
Pharmaceutical Suspensions:

1. Nature of suspended material: The interfacial properties of the suspended material
are an important consideration during the formulation of a suspension.
Particles that have low interfacial tension are easily wetted by water and therefore
can be suspended easily. Particles of materials with high interfacial tension,
however, are not easily wetted. The suspension of such materials is normally
achieved by using surfactants. Surfactants increase wettability of the particles by
reducing their surface tension.

2. Size of suspended particles: Reduction of particle size leads to a decrease in the
rate of sedimentation of the suspended particles as explained by Stoke’s law.
Reduction in the size of particles can be achieved by processes such as milling,
sieving, and grinding. Particle size also affects rate and extent of absorption, dissolution,
and biodistribution of the drug. However, reducing particle size beyond
a certain limit may lead to formation of a compact cake upon sedimentation.

3. Viscosity of the dispersion medium: Greater viscosity of dispersion medium
offers the advantage of slower sedimentation; however, it may compromise other
desirable properties such as syringability for parenteral suspensions, spreadability
for topical suspensions, ease of administration for oral suspensions. The
property of shear thinning is highly desirable so that the suspension is highly
viscous during storage when minimal shear is present so that the sedimentation
is slow and has low viscosity after agitation (high shear) to facilitate ease of
pourability from the bottle.

Sustained Release Suspensions:
Emphasis has been placed lately on achieving sustained release of drugs by using pharmaceutical suspensions.
Sustained release of drugs can be achieved after injection through intramuscular or subcutaneous route because
of limited availability of dissolution medium. The particle size of suspension can be tailored
to fall in colloidal or coarse range, depending on a variety of factors such
as type of drug, formulation, site of action, and route of delivery. Depending on
the aqueous solubility, the drug can be delivered in conjugation with polymers
or metal salts to sustain the release (Morales et al. 2004; Gietz et al. 2000).
Polymers can efficiently alter drug release kinetics through encapsulation or
conjugation of the drug. A variety of microparticulate or nanoparticulate delivery
vectors can be prepared that can efficiently prolong the release of drug.
These systems will be discussed later in the chapter. Addition of metal salts
cause aggregation of drug molecules by formation of metal-hydroxy and -oxy
polymers (Masuoka et al. 1993). This strategy has traditionally been used for
precipitation of insulin and corticotrophin and more recently to achieve sustained
release of recombinant hirudin (Gietz et al. 1998).