PharmaWallah
Get app

Pharmaceutics

Isotonicity Calculator

Uses sodium chloride equivalents (E-values) to check whether an eye drop or injection is isotonic, and how much sodium chloride to add if it is not.

Sodium chloride to add

0.748g per 100 mL

HYPOTONIC — May cause irritation · NaCl equivalent 0.15%

Isotonicity results

TonicityHYPOTONIC
May cause irritation
Total NaCl equivalent, Σ(C × E)0.15%
NaCl to add0.748%per 100 mL
Freezing point-0.09°C
Osmolality49mOsm/kg

Tonicity scale

0.15%
0% (Water)0.9% (Isotonic)1.8% (Hypertonic)

Formulation ingredients

Each ingredient's concentration and E-value. Rows missing either value are left out of the total.

Add a common ingredient (at 1% w/v)

Try an example

Working

Each counted ingredient converted to % w/v and multiplied by its E-value.

Active Drug1% × 0.15 = 0.15% NaCl
Benzalkonium Chloride0.01% × 0.16 = 0.0016% NaCl
Sodium Chloride0% × 1 = 0% NaCl

Formulation instructions

To make this formulation isotonic, add 0.748 g of sodium chloride per 100 mL.

Alternatives: Dextrose 4.16%, Glycerin 2.20%, Boric acid 1.50%.

Common E-values

Sodium Chloride1.00
Dextrose0.18
Boric Acid0.50
Glycerin0.34

Worked example: adjusting a phenylephrine eye drop to isotonicity

A compounding exercise gives 15 mL of eye drops containing phenylephrine hydrochloride 1% w/v and benzalkonium chloride 0.01% w/v as preservative. How much sodium chloride makes the drops isotonic? (Illustrative formulation for a calculation exercise — not a prescribing recommendation.)

Phenylephrine HCl
1 % w/v, E = 0.32
Benzalkonium chloride
0.01 % w/v, E = 0.16
Sodium Chloride row
0 % w/v, E = 1.00
Batch volume
15 mL

  1. NaCl equivalent of each ingredient (C × E)

    Phenylephrine HCl: 1 × 0.32 = 0.32 Benzalkonium chloride: 0.01 × 0.16 = 0.0016

  2. Total NaCl equivalent

    Σ(C × E) = 0.32 + 0.0016 = 0.3216 % (shown as 0.32%) → HYPOTONIC

  3. NaCl still needed per 100 mL

    0.9 − 0.3216 = 0.5784 → 0.578 g per 100 mL

  4. Scale to the 15 mL batch (by hand)

    0.578 g × 15 mL ÷ 100 mL = 0.0867 g ≈ 86.7 mg

  5. Check in the calculator

    Enter 0.578 in the Sodium Chloride row: Σ = 0.3216 + 0.578 = 0.8996 % → 0.90%, ISOTONIC

Add 0.578 g of sodium chloride per 100 mL — about 86.7 mg for the 15 mL batch.

Before the adjustment the calculator shows NaCl equivalent 0.32%, HYPOTONIC, freezing point −0.19 °C and an estimated 104 mOsm/kg; the 'NaCl to add' card reads 0.578 g per 100 mL. The calculator works per 100 mL, so scaling to the batch volume is your step. Whether a real product is acceptable is decided by measured osmolality, not by this estimate.

Common mistakes

Forgetting to scale: the result is grams of NaCl per 100 mL, so a 15 mL or 30 mL batch needs proportionally less.
Leaving out minor ingredients. Preservatives, buffers and other salts all contribute to tonicity; boric acid at 1.9% alone is roughly isotonic.
Entering mg/mL as if it were % w/v. 10 mg/mL is 1% w/v — the unit selector converts, but typing the mg/mL number into a % row makes it ten times too large.
Using an E-value for the wrong salt or hydrate, or one listed for a very different concentration. E-values change slightly with concentration; pick the tabulated value closest to yours.
Adding sodium chloride when the drug is incompatible with it (some silver and other salts precipitate with chloride). Use another tonicity agent at the equivalent strength — dextrose, for example, at NaCl to add ÷ 0.18.

Assumptions and limitations

The sodium chloride equivalent method assumes the osmotic contributions of the ingredients simply add, and that 0.9% w/v NaCl is the isotonic reference. It is an approximation; measured freezing point or osmolality is the real test.
The freezing point and osmolality shown are scaled from the NaCl equivalent (0.9% ≈ −0.52 °C ≈ 290 mOsm/kg), not calculated from first principles.
Isotonic is not the same as iso-osmotic: a solute that crosses cell membranes freely (boric acid for red cells, for example) can be iso-osmotic yet not isotonic.
The mM entry option uses a very rough fixed factor; enter concentrations in % w/v or mg/mL wherever you can.

Keep learning

Guide: Dilution and Concentration CalculationsThe concept in full, with practice questions.Percentage Solution Calculator (w/v, w/w, v/v)Work out the weights of each ingredient for the batch from their % w/v.Dilution Calculator (C₁V₁ = C₂V₂)Prepare the drug from a concentrated stock before adjusting tonicity.

References

  1. Stockton SJ. Stoklosa and Ansel's Pharmaceutical Calculations. 16th ed. Philadelphia: Wolters Kluwer; 2021.
  2. Sinko PJ, editor. Martin's Physical Pharmacy and Pharmaceutical Sciences. 8th ed. Philadelphia: Wolters Kluwer; 2023.
  3. United States Pharmacopeia–National Formulary. General Chapter <785> Osmolality and Osmolarity. Rockville (MD): USP.

Common questions

Prepared by the PharmaWallah student team. Verify results with your textbook or instructor. Report an error · Editorial policy