Tonicity Adjustment Database

Last Review: January 2006

For comfort during administration, many dosage forms must be "isotonic" with body fluids. This is especially true of parenterals, ophthalmics and nasal solutions. Pain and irritation at the site of administration may occur if the formulation is either hypertonic or hypotonic.

Tonicity is the 'effective osmolality' and is equal to the sum of the concentrations of the solutes which have the capacity to exert an osmotic force across the membrane

Hypotonicity is a property that can be addressed by the compounding pharmacist; hypertonicity can be addressed, if it is possible to decrease the concentration of some components of the formulation.

Biologic systems are compatible with solutions having similar osmotic pressures, i.e., an equivalent number of dissolved species. For example, red blood cells, blood plasma and 0.9% sodium chloride solution contain approximately the same number of solute particles per unit volume and are termed iso-osmotic and isotonic. If solutions do not contain the same number of dissolved species, i.e., they contain more (hypertonic) or less (hypotonic), then it may be necessary to alter the composition of the solution to bring them into an acceptable range.

The USP 29-NF 24 lists five excipients classified as "tonicity" agents, including dextrose^(1,2), glycerin^(1,3), mannitol^(1,4), potassium chloride^(1,5) and sodium chloride^(1,6).