Tonicity Adjustment Database

Last Review: January 2006

Select an agent by clicking on the name
Dextrose Glycerin Mannitol
Potassium Chloride Sodium Chloride

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).

Source Reference
1.United States Pharmacopeial Convention, Inc. United States Pharmacopeia 29-National Formulary 24. Rockville MD: U.S. Pharmacopeial Convention, Inc.; 2005: 3261.
2.Day, A. Dextrose. In: Rowe RC, Sheskey PJ and Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington DC: American Pharmaceutical Association; 2005: 231-233.
3.Price JC. Glycerin. In: Rowe RC, Sheskey PJ and Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington DC: American Pharmaceutical Association; 2005: 301-303.
4.Armstrong NA. Mannitol. In: Rowe RC, Sheskey PJ and Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington DC: American Pharmaceutical Association; 2005: 449-453.
5.Owen SC. Potassium Chloride. In: Rowe RC, Sheskey PJ and Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington DC: American Pharmaceutical Association; 2005: 600-602.
6.Owen SC. Sodium Chloride. In: Rowe RC, Sheskey PJ and Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington DC: American Pharmaceutical Association; 2005: 671-674.