Adjustment of isotonicity

And Dissociation Factor

By:
Amir Musa Omar
The dissociation factor is a measure of the extent of
ionization of a chemical such as the drug substance.
The extent of ionization is important because it effects the osmotic
pressure.

Osmotic pressure is a colligative property and is dependant on the

number of particles of solute(s) in solution.
The total number of particles of a solute in a solution is the sum of
the undissociated molecules and the number of ions into which
the molecule dissociates.

The number of ions, in turn, depends on the degree of ionization.

The chemical that is highly ionized contribute a greater number
of particles to the solution than the same amount of poorly
ionized chemical.

When a chemical is none electrolyte such as sucrose or urea, the

concentration of the solution depends only on the number of
molecules present.

The values of the osmotic pressure and other colligative

properties are approximately the same for equal concentrations
of different nonelectrolyte solutions.

The dissociation factor symbolized by the litter (i), can be

calculated by dividing the total number of the particles
(Which include undissociated molecules and ions) in a solution by
the number of particles before dissociation

Example:

what is the dissociation factor of KCl, having 60% dissociation in

water?
Assume that we have 100 particles of KCl prior. Upon 60%
dissociation, 100 molecules of potassium chloride yield:
Example 2:
What is the dissociation factor of magnesium sulfate, having 80%
dissociation in water?
Assume that we have 100 particles of magnesium sulfate prior to
dissociation.
Upon 80% dissociation, 100 molecules of magnesium sulfate yield:
80 magnesium ions
80 sulfate ions
20 undissociated magnesium sulfate particles
= 180 total particles in solution

I = 180 = 1.8
100
Example 3:
What is the dissociation factor of sodium carbonate Na2CO3 , having
60% dissociation in water?
Assume that we have 100 particles of sodium carbonate prior to
dissociation. Upon 60% dissociation, 100 molecule of sodium
carbonate yield:
120 (60x2) sodium ions
60 carbonate ions
40 undissociated sodium carbonate
= 220 total particles in solution

I = 220/100 = 2.2
 SODIUM CHLORIDE EQUIVALENTS
OF DRUG SUBSTANCES

by definition, the sodium chloride equivalent of a chemical is the

amount of sodium chloride (in grams or grains) that has the same
osmotic pressure as that of 1 gram of the chemical.

The sodium chloride equivalents are symbolized by the letter E.

The E value can be found in standard tables that can be found in

many pharmaceutics and calculations texts.
The E value can be calculate, if molecular weight and
dissociation factor values are known, by the following
equation
Example:
Calculate the sodium chloride equivalent of 1% solution of
chlorbutanol. Chlorbutanol has a molecular weight of 177 and I of 1
ISOTONICITY ADJUSTMENTS BY SODIUM
CHLORIDE EQUIVALENT METHOD

The sodium chloride equivalent method is the most commonly

used method for isotonicity adjustments.

The sodium chloride (in g) equivalent of any drug substance, as

discussed earlier, is the amount of sodium chloride that is
osmotically equivalent to 1 gram of the drug.
The sodium chloride equivalent for selected compounds are
calculated.

Any hypotonic solution containing one or more drugs can be

rendered isotonic by adding an appropriate quantity of sodium
chloride.

Extreme care is needed for isotonicity adjustments of hypertonic

solutions.

If water is added to convert the hypertonic solution to an isotonic

solution, the drug concentration will decrease and additional
drug will have to be added.

Therefore, isotonicity adjustments usually are done for hypotonic

solutions
Following is a sample prescription that requires isotonic
adjustments
In the prescription, 1% naphazoline is ordered.

The sodium chloride equivalent of naphazoline HCl is 0.27 (refer

to the calculated value).

This means that 1% solution of naphazoline HCl has the same

osmotic pressure as that of 0.27% solution of sodium chloride.

This solution is hypotonic.

Addition of 0.63 g (i. e., 0.9 – 0.27 = 0.63) of sodium chloride per
100 ml of the 1% solution of naphazoline hydrochloride results in
an isotonic solution
To determine the amount of sodium chloride required to render a
given solution isotonic, the following steps may be used

Step 1. determine how much sodium chloride is needed to

render the formulation isotonic for body fluids
(Remember isotonicity refers to 0.9% or 0.9 g/ 100 ml).
Step 2. find the amount of sodium chloride represented by the
ingredients in the prescription by multiplying the quantity of
each ingredient by its E value.

Add up all the values obtained.

This is the total amount of sodium chloride represented by all

the ingredients in the prescription.
Step 3. subtract the total value obtained in Step 2 from the
amount of sodium chloride required to render the formulation
isotonic (i. e. the value obtained in Step 1).

The value obtained in this step represents the amount of

sodium chloride required to be added to render the solution
isotonic
Find the quantity of sodium chloride required in
compounding the following prescription. The sodium chloride
equivalent of sulfacetamide sodium is 0.23.

0.2 Sulfacetamide Sodium

q. s Sodium Chloride
30 ml Purified water ad

Make isotonic Solution

Sig. one drop in each eye

0.224 g, answer
Find the quantity of sodium chloride to be used in
compounding the following prescription. The sodium
chloride equivalent of chlorbutanol is 0.18.

0.5 Chlorobutanol
q. s Sodium Chloride
50 ml Purified water to
Make isotonic Solution
Sig. Use as directed

answer = 0.36 g,
 Find the quantity of sodium chloride to be used in
compounding the following prescription. The values of
sodium chloride equivalent of glycerine and scopolamine
HBr are 0.34 and 0.12 respectively.

1% Glycerine
0.50% Scopolamine HCl
q. s Sodium Chloride
60 Purified water

Make isotonic Solution

Sig. use in the eye

answer = 0.30 g,
Find the quantity of boric acid (in grams) to be used in
compounding the following prescription.

0.50% Atropine Sulfate

q. s Boric Acid
30 ml Purified water ad to
Make isotonic solution

answer = 0.483 grams,

Find the quantity of boric acid (in grams) to be used in
compounding the following prescription.

0.1 Chlorobutanol
0.05 Zinc Sulfate
q. s Boric Acid
30 ml Purified water add to
Make isotonic solution, Sig: drop in
eye

(answer = 0.471 grams,)

How many grams of dextrose should be used in
compounding the prescription?

0.5 Sulfacetamide Sodium

0.25 Chlorobutanol
q.s Dextrose
50 ml Rose water add
Make isotonic solution, sig: Nose drops

answer = 1.812 g,