KOMAR UNIVERSITY

OF SCIENCE AND TECHNOLOGY

Monica Diyya,
Department of Pharmacy,
College of Medicine.
 Course Name: Physical Pharmacy-I

UNIT IV: Buffers and Buffered Isotonic solutions

Lesson No: 04B-Isotonicity-Methods to adjust

Isotonicity
 Contents

Isotonic Solutions
• Isotonicity-Introduction
• Isotonic Solutions
• Methods of Adjusting Tonicity
 ISOTONICITY

➢Two solutions are said to be iso-osmotic or isotonic if

they exert the same osmotic pressure when two
separated by a semi-permeable membrane.

➢Physiologically, isotonic solutions are solutions having

the same osmotic pressure as that of the body fluids
when separated by a biological membrane.

➢Body fluids including blood and lachrymal fluid,

normally have an osmotic pressure corresponding to
that of 0.9% solution of sodium chloride.

➢Thus, 0.9% solution of sodium chloride is said to be

isotonic with the physiological fluids.
➢Solutions with osmotic pressure lower than that of
the body fluids or of 0.9% sodium chloride solution
are referred to as hypotonic and those having a
higher osmotic pressure are termed as hypertonic.

• If red blood cells are suspended in a hypertonic

solution, the water within the cells passes out
through the cell membrane in order to dilute the
surrounding salt solution and attain an equilibrium
across the membrane.

This outward passage of water causes the cells to

shrink and become wrinkled or crenated.
• If red blood cells are suspended in a hypotonic solution,
water enters the blood cells causing swelling and finally
bursting of the cell with the liberation of haemoglobin.
This bursting of cells is known as haemolysis.

Thus, hypotonic solutions, if injected into the blood

stream will cause haemolysis of red blood cells while
hypertonic solutions may cause shrinkage of red blood
cells.
Paratonic solutions (hypertonic or hypotonic) if
instilled into eyes or nose may cause irritation
specially if the quantity instilled is large.

Pharmaceutical solutions that are meant to be

introduced into the body or applied to the
delicate membranes of the body should be
isotonic with the physiological fluids (blood
plasma, lachrymal secretion).

Parenteral, ophthalmic and nasal preparations

are therefore made isotonic by adding
therapeutically inert substances like sodium
chloride, dextrose, etc. into the preparations.
 Methods Of Adjusting Tonicity

➢In order to render a hypotonic solution, isotonic

with the body fluids, substances such as sodium
chloride and dextrose are added to it.
➢Alternatively, water is added to a drug
substance in sufficient amount to form an
isotonic solution which is further diluted with an
isotonic or a buffered isotonic solution to give
the final volume.
The following methods are generally followed for
adjustment of tonicity.
 Methods of adjusting Tonicity and pH
Method Name of the method

Class-1 1. Cryoscopic method

¥
Methods 2. Sodium chloride equivalent
method
Class-2 1.White Vincent method

:&
Methods 2. Sprowls method

Class-3 Freezing point depression and L-iso

Methods values for number of drugs are
estimated theoretically from the
molecular weight of the drug and
can be used to calculate the amount
of adjusting substance to be added
in order to make the solution
isotonic.
*
1. Cryoscopic or Freezing point depression method
Body fluids such as blood plasma and lachrymal
secretion have a freezing point of -0.520C by virtue of
the different solutes present in them.

§ della ΔTf of blood = 0.520C

Hence all solutions which freeze at -0.520C will be
isotonic with these fluids.
Point

¥
-

Depression in freezing point being an additive

property, the following formula is used for the
calculation of the quantity of a substance required to
make solution isotonic with physiological fluids.
𝟎. 𝟓𝟐 − 𝒂
%w/v of adjusting substance =
𝒃
Where,
a = depression in freezing point due to the unadjusted
solution or substance.
b = depression in freezing point of 1% w/v of adjusting
substance.
Practical problem No.1
o
How much % w/v of NaCl is required to render 100 mL of a
1% solution of apomorphine HCl isotonic with blood
✗
od
serum?(1% solution of the drug has a ∆Tf of 0.08°C;1%

←
solution of NaCl has a ∆Tf of 0.58°C)
.

Solution: a
𝟎. 𝟓𝟐 − 𝒂
%w/v of adjusting substance =
𝒃
Here, a=0.08
write + Parameter
b= 0.58 eq fuy
%w/v of NaCl required(adjusting substance) = (0.52-
0.08)/0.58 name

ÉÉa•+
= 0.758.
0.758%w/v of NaCl is required to make the drug solution
isotonic with blood. -

to unitethis
2. Sodium Chloride equivalent Method or Tonicity
equivalent Method

The sodium chloride equivalent or tonicity equivalent

of a drug is the amount sodium chloride that is
equivalent to 1 gram of the drug osmotically.
The sodium equivalent, E can be found in the
literature.
The % of NaCl required for adjusting the isotonicity can
be calculated using the following equation:

PSA = 0.9-(PSM X E of medicament)

↓
Where, Nac

PSM= Percent strength of medicament

PSA=Percent of sodium chloride for the adjustment of
isotonicity
 can be Asked
Practical problem No.2
.

A solution contains 1.0 g of ephedrine sulfate in a

volume of← 100 mL. What quantity of sodium chloride

to
must be added to make the solution isotonic? E
value for the drug is 0.23.
Solution:
PSA = 0.9-(PSM X E of medicament)

= 0.9- (1x0.23)
= 0.67
0.67g of sodium chloride is required to make the drug

☆
solution isotonic.
 Practical problem No.3
Calculate the gram of sodium chloride needed to make
30mL of a 2% isotonic physostigmine salicylate solution
using sodium chloride method.
(E value of Physostigmine salicilate= 0.16)
Solution:
E value of Physostigmine salicilate= 0.16
PSM=2.0%

:[
Volume of the preparation required=30mL
PSA = 0.9-(PSM X E of medicament)
=0.9-(2 x 0.16)

.÷÷
= 0.9-0.32 = 0.58% (for 100mL)
For 100mL of solution, sodium chloride required = 0.58
For 30mL of solution, sodium chloride required = ?
= 30x0.58/100 = 17.4/100 = 0.174g of sodium chloride.
0.174g of sodium chloride is required to make 30mL of given
drug solution isotonic.
 3.White Vincent Method

The class II methods of computing tonicity involve the

addition of water to the drugs to make an isotonic
solution, followed by the addition of an isotonic-
buffered diluting vehicle to bring the solution to the
final volume.
White and Vincent developed a simplified equation
for calculating the volume V (mL) of isotonic solution
prepared by mixing the drug with water.

tho 𝑽 = 𝒘 × 𝑬 × 𝟏𝟏𝟏. 𝟏
V : required volume of water to be added
w : weight (g) of the drug.
E : NaCl equivalent
 Practical problem No.4

How to make 30 mL of a 1% solution of procaine HCl

isotonic with body fluid? NaCl equivalent for procaine
HCl is 0.21
Solution:
Weight of the drug = 30 × 1% = 0.3 g
-

iii.÷;¥
-

𝑽 = 𝒘 × 𝑬 × 𝟏𝟏𝟏. 𝟏

𝑽 = 0.3 × 0.21 × 111.1 = 7 ml

dong
-
-

o¥-
7 ml of water is added to the drug to make it isotonic,
then enough isotonic diluting solution is added to make
30 mL of the finished product.
 4. Sprowls method

Sprowls method is a simplification of White-Vincent

Method in which V values for drugs of fixed weights (0.3
g) are computed and constructed as a table.
‘W is kept constant as 0.3’
 5. Liso Method

Liso value is the isotonicity lowering value which is the

correction factor for freezing point.
In this method, freezing point depression is used to
calculate the amount of the isotonicity adjusting substance
that must be added to hypotonic solution of drug to bring
to tonicity.
ΔTf = Liso C
Where,
C = molarity/litre
ΔTf = Liso x W x [1000/(Mw x V)]

If the concentration of the drug is chosen to be 1%, then ∆Tf

of can be theoretically by the equation:
∆𝑻𝒇 = 𝑳𝒊𝒔𝒐 x 10/M.wt
The sodium chloride equivalent (E) of a drug is the
amount of sodium chloride that has the same
osmotic effect of 1 g of the drug.
E value can be obtained theoretically from Liso value
and Molecular weight of the drug.

𝑳𝒊𝒔𝒐
𝑬 = 𝟏𝟕
𝑴. 𝑾𝒕

Practical Problem No.5

Calculate the approximate E value for ephedrine
sulfate (M.Wt=428.54) (Liso = 5.8)

E- -
17
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