Method of

adjusting Tonicity

continuous

Method of adjusting
Tonicity
Class I Method
u The cryoscopic
method
u The Sodium
Chloride
Equivalent method.

Class I I Method
u White-Vincent
Method.

Class I Method
1-Cryoscopic Method
u Freezing

point depression method

u The calculations, involved in the
cryoscopic method are explained
best by an example

1-Cryoscopic Method
Example
How much sodium chloride is required
to render 100 ml of a 1 % solution of
apomorphine hydrochloride isotonic
with blood serum?

Cryoscopic Method
1 % solution of the drug has a freezing
point lowering of 0.08 .
u To make this solution isotonic with blood,
sufficient sodium chloride must be added
to reduce the freezing point lowering to
that of a 1 % solution of sodium chloride
which has a freezing point lowering of 0.58
u 0.52 - 0.08= 0.44
u

Cryoscopic Method
u By

the method of proportion.

= 0.52C
X= 0.76%
u 0.9%
X
0.44C
u Thus,

0.76 % sodium chloride will

lower the freezing point to the
required and will render the solution
isotonic.

Cryoscopic Method
u The

solution is prepared by
u dissolving 1.0 gm of apomorphine
hydrochloride and
u 0.76 gm of sodium chloride in
u sufficient water to make 100 ml of
isotonic solution.

2-Sodium Chloride
Equivalent Method
The Sodium Chloride Equivalent (E)
(E) of
a drug
is the amount of sodium chloride
which has the same osmotic effect as
1 gram of the drug
drug..

TABLE OF SODIUM CHLORIDE

EQUIVALENTS
Substance

Molecular
weight

Ions

Sodium chloride
equivalent E

Boric acid

61.8

0.52

cocaine
hydrochloride

340

0.17

ephedrine sulfate

429

0.2

2-Sodium Chloride Equivalent

Method
For determining the amount of sodium chloride
used to cause a solution isotonic,

multiply the quantity of each drug in the

prescription by its sodium chloride equivalent E ,

and subtract this value from the concentration of

sodium chloride which is isotonic with body fluids
(0.9 gm per 100 ml).

2-Sodium Chloride Equivalent

Method
Example :
A solution contains 1 gm of
ephedrine sulfate in a volume of 100
ml, what quantity of sodium chloride
must be added to make the solution
isotonic ? How much dextrose would
be required for this purpose?
NaCl equivalent (E) of Ephedrine
sulfate is 0.23

1 gm of Ephedrine sulfate is osmotically

equivalent to 0.23 gm NaCl
u 1.0 gm X 0.23 = 0.23 gm
u Since a total of 0.9 gm of sodium chloride
is required for isotonicity of 100 ml
solution
u 0.90 0.23 = 0.67 gm of NaCl must be
added.

Dextrose
u If it is desired to use dextrose instead of
sodium chloride for adjusting the tonicity.
u the sodium chloride equivalent of dextrose
= 0.16
u 1gm dextrose =
0.16 gm NaCl
u X gm dextrose =
0.67 gm NaCl
u X = 4.2 gm of dextrose
u

Class I I Method
White--Vincent Method.
White

White--Vincent Method.
White

It involves the addition of water to the

drugs to make an isotonic solution.

White--Vincent Method.
White
u Example

:
u
To make 30 ml of a 1 % solution of
cocaine hydrochloride isotonic with
body fluid.

Class I I Method

White--Vincent Method.
White
u The

weight of the drug is multiplied

by the sodium
u
chloride equivalent E
u
0.3 gm X 0.16 =0.048 gm
u
This is the quantity of sodium
chloride osmotically equivalent to
0.3 gm of cocaine hydrochloride.

Class I I Method
White--Vincent Method.
White
It is known that 0.9 gm of sodium chloride
in 100 ml water yields isotonic solution.
The volume V of isotonic solution which
can be prepared from 0.048 gm of sodium
chloride
u
(equivalent to 0.3 gm of cocaine
hydrochloride)
u

V = w X E X 111.
111.1

Class I I Method
White--Vincent Method.
White
u
u
u
u
u
u
u
u
u

100/0.9 = 111.
100/
111.1
V = the volume in ml of isotonic solution which may be
prepared by mixing the drug with water
w = the weight in grams of the drug given in the problem,
E = the sodium chloride equivalent obtained from Table
111..1= the volume in ml of isotonic solution obtained by
111
dissolving 1 gm of Sodium Chloride in water.
V = 0.3X 0.16 X 111
111..1
V = 5.3 ml

Class I I Method
White--Vincent Method.
White
u In

order to complete the isotonic

solution to make
u 30 ml of the finished product, enough
isotonic sodium chloride
u solution, or an isotonic-buffered
solution is added.

Example :
Make the following solution isotonic with respect to an
ideal membrane.
R/
Phenacaine hydrochloride
0.06 gm
Boric acid
0.30 gm
Sterilized distilled water to
100 ml
V = W X E X 111
111..1
V = W X E X 111
111..1 = [(0
[(0.06 X 0.18
18)) +(0
+(0.3 X 0.50
50)]
)] X 111
111..1
V = 17
17..7 ml
The drugs are mixed with water to make 17
17..7 ml
of an isotonic solution and the preparation is completed
with isotonic solution to make 100 ml of the finished
product.

GOOD LUCK