Liquid dosage forms

Sedimentation is governed by gravity and by the size and density of the suspended particles. Left standing, the particles of a suspension sink; the liquid near the top becomes poorer in drug and the layer at the bottom becomes richer. Two consequences follow. First, a dose poured without shaking contains less active ingredient than intended, so the infection or the symptom is under-treated while the patient believes the medicine was taken. Second, when the bottle is nearly empty, the concentrated sediment at the bottom can deliver far more drug than intended, turning an ordinary dose into a potential overdose. Shaking redisperses the sediment and restores a uniform suspension. The vocabulary is worth keeping: sedimentation is the settling, redispersion is the return to a uniform state, and a suspension is described as sufficiently stable when it can be redispersed well enough to deliver the correct dose. The misconception to correct is that shaking is a habit copied from tradition. It is a dosing step with a measurable effect on the amount of drug delivered, which is why labels state it explicitly and why a caregiver should be shown how to do it. Note also what does not need shaking: a true solution is homogeneous and its composition is the same throughout the bottle.

Water is a good solvent, and that is precisely the problem: it also favours chemical breakdown and microbial growth. The lecture notes list the major signs of instability in liquid preparations as a change in colour, odour, viscosity or taste, precipitation, microbial growth and chemical gas formation. Each sign has a mechanism behind it. A change of colour or odour usually means a chemical reaction, often oxidation, has altered the molecule. Precipitation means the drug has come out of solution, so the dose in the liquid is no longer the dose on the label. Gas formation means a reaction is producing a volatile product. A change in viscosity or taste points to physical or chemical change in the vehicle or the active ingredient. Microbial growth is possible because a solution is a suitable medium for micro-organisms, which is why a preservative may be added. A beginner’s misconception is that a clear liquid is necessarily a good liquid, or that a preparation is safe until the printed date regardless of how it has been stored or handled. Storage conditions, the addition of water during reconstitution, and whether a preservative is present all change the real shelf life. In practice, inspect before dispensing, teach the patient to inspect before each dose, and discard a liquid that shows any of these signs rather than trying to judge its strength by eye.