Isotonic Solutions

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Isotonic Solutions
 ISOTONIC solutions cause no swelling or contraction of the tissues with
which they come in contact, and produce no discomfort when instilled in
the eye, nasal tract, blood, or other body tissues.

 Outward passage of water causes the cell to shrink and become

WRINKLED or CRENATED. The salt solution is said to be
HYPERTONIC.

 When water enters the blood cells, it causes them to swell and finally
burst, and hemoglobin liberated, this is called HEMOLYSIS, solution is
HYPOTONIC.

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 Isotonic Solutions

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Measurement of Tonicity:

It is now well established that -0.52 is the freezing point

of both human blood and lacrimal fluid. This temperature
corresponds to the freezing point at a 0.9% NaCl solution,
which is therefore considered to be isotonic with both
blood and lacrimal fluid.

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Calculating Tonicity Using Liso Values:

 A new factor is introduced for the freezing point depression of

electrolytes which is ( L = i Kf )
Tf = i Kf m  Tf = Lc where: L = i Kf
c = molar concentration
 Specific Liso value is obtained from the freezing point lowering of
solutions at representative compounds of a given ionic type at a
concentration (c) that is isotonic with body fluids.
 Liso: L value for the concentration which is isotonic with body
fluids.
e.g.: the Liso value for a 0.9% (0.154M) solution of NaCl which has a
freezing point depression of 0.52, and is thus isotonic with body
fluids is 3.4.

Tf 0.52
Liso value =  Liso = = 3.4
c 0.154
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The interionic interaction in solutions that are not too concentrated is

roughly the same for all uni-univalent electrolytes (same Liso value)
regardless of the chemical nature.

Example (8-11) page 181 (fourth edition)

Example (9-11) page 222 (fifth edition)
What is the freezing point lowering at a 1% solution of Na
Propionate (Mw= 96)?
Na Propionate is uni- uinvalent; its Liso value is 3.4.
The molar concentration of a 1% solution of this compound
is
10
c= = 0.104.
96

Tf = 3.4  0.104 = 0.35

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 L value

Liso values of various ionic classes

Calculating Tonicity Using Liso Values:

Table – average Liso values for various ionic types

Type Liso Examples

Nonelectrolytes 1.9 Sucrose, glycerin, urea
Weak electrolytes 2.0 Boric acid, phenobarbital
Di-divalent electrolyte 2.0 Magnesium sulphate, zinc sulphate
Uni-univalent electrolyte 3.4 Sodium chloride
Uni-divalent electrolyte 4.3 Sodium sulphate, atropine sulphate
Di-univalent electrolyte 4.8 Zinc chloride, calcium bromide
Uni-trivalent electrolyte 5.2 Sodium citrate, sodium phospate
Tri-univalent electrolyte 6.0 Aluminum chloride, ferric iodide
Tetraborate electrolyte 7.6 Sodium borate, potassium borate

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Methods for adjusting tonicity:

 Class 1: Cryoscopic Method and NaCl

Equivalent Method.

 Class 2: White-Vincent Method (water is added

to the drug in sufficient amount to form an
isotonic solution).

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Cryoscopic Method:

- Based on the calculation of Tf of the solution and how

much NaCl should be added to make:
Tf (solution) = Tf (blood)

- Tf1% = Tf for 1% concentration, and this value is

listed in tables for many drugs.

- If we know the M.Wt of the drug and the Liso value of

the ionic class, we can calculate the freezing point
depression.
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Example: How much NaCl should be added to 1%
apomorphine.HCl solution to make it isotonic with blood?

From tables: Tf1% for the drug = 0.08

Tf for the drug should be = 0.52
 0.52 - 0.08 = 0.44 (to be lowered)
If 0.9gm NaCl in 100ml have 0.52 Tf , thus for 0.44

0.9  0.44
 = 0.76gm NaCl that should be added to
0.52
the 100ml solution.

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Sodium Chloride Equivalent Method:

NaCl Equivalent (E): the amount of NaCl that is
equivalent to (ie. Has the same osmotic effect as) 1gm, or
other weight unit, of the drug.

Liso
E  17  M.Wt

Example: calculate the appropriate E value for a new

amphetamine hydrochloride derivative (M.Wt = 187).
The drug is uni-univalent salt, it has an Liso value of 3.4.
Its E value calculated for equation to be:

E = 17  3.4 = 0.31
187
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White-Vincent Method:
It involves the addition of water to the drugs to make an
isotonic solution, followed by the addition of an isotonic or
isotonic-buffered diluting vehicle to bring the solution to the
final volume.

Used when certain volume of isotonic solution is to be

prepared then diluted with already available isotonic solution.

V = w  E  111.1

V: volume in milliliters of isotonic solution that may be

prepared by mixing the drug with water.
w: the weight of the drug in grams.
E: NaCl equivalent (from tables).
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Example (8-16) page 186 (fourth edition)

Example (9-16) page 228 (fifth edition) :
Make the following solution isotonic with respect to an ideal
membrane.
Phenacaine Hydrochloride . . . . . . . . . . . . . . . . . . 0.06 gm
Boric Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.30 gm
Sterilized Distilled Water, enough to make . . . . . . 100.0 ml
Solution:
V =  [w  E  111.1]
= [(0.06  0.20) + (0.3  0.50)]  111.1
= 17.998 ml H2O  18 ml
 dissolve the two drugs in 18 ml H2O  isotonic solution, then
add isotonic solution to make the volume 100 ml (82 ml isotonic
solution).

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