Isotonicity — sodium chloride equivalent (E value)

Calculate a drug's sodium chloride equivalent and the amount of sodium chloride needed to make a solution isotonic.

What is this for?

The sodium chloride equivalent (E value) is the weight of sodium chloride that produces the same osmotic effect as 1 gram of the drug. It converts any drug into "sodium chloride units", which lets you work out how much additional sodium chloride is needed to reach the 0.9% w/v that is isotonic with blood and tears.

How to use it

Enter the molecular weight of the drug and its dissociation factor i. Published E values exist for most drugs — use them in preference to calculating when available.
To find the E value alone, stop there.
To solve a full isotonicity problem, also enter the drug concentration as % w/v and the volume you are preparing. The result gives the grams of sodium chloride to add.

Worked example

Prepare 30 mL of a 1% w/v solution of a drug with molecular weight 337.4 that dissociates into two ions. How much sodium chloride is needed to make it isotonic?

Answer: E = (58.5 × 1.8) ÷ (337.4 × 1.8) = 0.173. The preparation contains 0.3 g of drug, contributing 0.052 g NaCl equivalent. Isotonic 30 mL needs 0.27 g NaCl, so add 0.27 − 0.052 = 0.218 g.

Clinical pearls & pitfalls

The 1.8 in the denominator is the dissociation factor of sodium chloride itself, and 58.5 is its molecular weight. The formula is simply comparing the drug's osmotic contribution to that of sodium chloride.
Use published E values when they exist. The calculated value assumes idealised dissociation and can differ from experimentally determined figures by several percent.
A negative "sodium chloride to add" means the drug alone is already hypertonic. This is common with high-concentration solutions and is a signal to reconsider the formulation, not to subtract salt.
Isotonicity matters most for ophthalmic, nasal, and parenteral routes. Substantial deviation causes stinging and, in the eye, corneal damage.

Assumptions & limitations

The dissociation factor i is an approximation based on the number of ions produced. Real dissociation is concentration-dependent and incomplete.
Calculates tonicity relative to 0.9% sodium chloride only. It does not evaluate compatibility, pH, buffering, or preservative requirements, all of which also determine whether an ophthalmic preparation is acceptable.
The E-value method assumes tonicity contributions are additive. This holds well at the dilute concentrations used in ophthalmics.

References

United States Pharmacopeia. General Chapter <1151> Pharmaceutical Dosage Forms — ophthalmic preparations.
Allen LV. The Art, Science, and Technology of Pharmaceutical Compounding. American Pharmacists Association.
Hammarlund ER, Pedersen-Bjergaard K. Sodium chloride equivalents, cryoscopic properties, and hemolytic effects of certain medicinals in aqueous solution. J Am Pharm Assoc. 1958;47(2):107-114.