A suspension is a heterogeneous system consisting of two phases, where solute particles do not dissolve, but uniformly dispersed throughout the bulk of the solvent.
Physical Stability
Before developing a suspension formulation, the physical stability of the drug in water should be checked, including temperature cycling if the drug has a temperature-dependent profile. More stable forms are less soluble so dissolution might be affected, in addition to other effects such as grittiness. In situ crystal growth can be exacerbated by water content, drug solubility and temperature fluctuations.
A functional structured vehicle should prevent sedimentation and flocculation but these are characteristic attributes of a suspension utilizing controlled flocculation. Floc volume and redispersibility should be included in the stability program for a controlled flocculation suspension.
Rheological characterization is more difficult for controlled flocculation suspensions as the structure resides within the floc rather than the vehicle. If samples on the rheometer settle during testing the rheology will reflect the supernatant rather than the floc. Drug content uniformity should be monitored by top, middle and bottom sampling of the vehicle and floc for structured vehicle and controlled flocculation suspensions respectively.
Chemical Stability
The chemical stability of a suspension is dependent on the specific drug but there are some general considerations. Gross instability in the presence of water is a contraindication to formulation as an aqueous suspension.
Because the drug is in suspension the stability will be generally be greater than if it were fully in solution, but less than if presented as a solid dose form.
As some of the drug will be in solution, buffer and/or sequestrant may be required if the drug exhibits pH-dependent stability or metal ion sensitivity.
Chemical stability may be worse in proportion to the water content of the suspension and dependent on how soluble the drug is in water. If the drug has a pH-dependent solubility profile, buffer may be required to minimize the amount of drug in solution.
If used, the stability of any preservatives must also be monitored, including both chemical degradation, and partition into plastic packaging.
