Isotonicity

PHT 434

osmosis
Osmosis is the diffusion of solvent through a semipermeable membrane.
Water always flows from lower solute concentration
[dilute solution] to higher solute concentration until a
balance is produced

Osmotic pressure is the force that cause this

diffusion .
Tonicity is a measure of the
osmotic pressure of two solutions
separated by a semi-permeable
membrane.

Types Hypotonic
of Tonicity isotonic
NaCl 0.2%

NaCl 0.9%

Hypertonic
NaCl 2%

solute

solute

solute

=solute

solute

solute

Inside

outside

Inside

outside

Inside

outside

swelling

equilibrium

shrinkage

?Why using isotonic solutions

Isotonicity & route of administration

Subcutaneous injection:

Hypodermoclysis

should be isotonic Large volume

Intramuscular injection

not necessarily small dose but isotonicity reduce pain.

should be isotonic or slightly hypertonic to increase

penetration

Intravenous injection

should be isotonic Large volume

Hypotonic cause haemolysis
Hypertonic solution may be administered slowly into a vein
Hypertonic large volume administered through a cannula into
large vessels.

.Isotonicity

Intrathecal injestion

Rapid diluted by tear, but most of it is isotonic to

decrease irritation

Eye lotions

Should be isotonic

Eye drops

& route of administration

Preferably isotonic

Nasal drops

Isotonic, but not essentially

cont

Classes of adjustment of isotonicity

Class I
Adding substace to lower f.p of solution to -0.52
1. Freezing point depression (FPD) cryoscopic
method.
2. NaCL equivalent method.

Class II
Adding H2O
3. White Vincent method

Freezing point depression (f.p.d)

Freezing Pointsolution = Freezing Pointsolvent - Tf
Tf =L c
L : constant , c : conc.(molarity)
It is Colligative property
Depend on concetration
same f.p.d
same conc.

same tonicity

0.9% NaCl is isotonic i.e. F.p.d = 0.52

Freezing point depression (FPD)- 1

. cryoscopic
method
F.P. of blood & tears
= - 0.52
Any solution have F.P. = - 0.52 is isotonic.
Any solution have F.P. - 0.52 is hypotonic
- 0.4 hypotonic
-0.6 hypertonic
Add solute to hypotonic solution to reach f.p.d
of blood (- 0.52 )

?How to calculate

0.52 a
w%
b

w%

a
b

= conc. gm/100 ml of adjusting substance

= f.p.d of 1% of unadjusted substance(table) X percentage strength

= f.p.d of 1% of adjusting substance (table)

Example I
How much NaCl is required to render 100 ml of
a 1% soln. of apomorphin HCL isotonic?
F.p.d of 1%NaCl=0.58, F.p.d of 1%drug=0.08

0.52 a
0.52 0.08
w%
w%
b
0.58
1% drug
1% NaCl
w% NaCl

w% 0.76%

0.08 (0.52- 0.08=0.44)

0.58
w% 0.76%
0.44

Example II
adjust isotonicity of procaine HCl 3% using
NaCl ? Fpd of 1%NaCl=0.57, f.p.d of 1%
drug=0.112

0.52 a
w%
b
w%

0.52 (0.112 * 3)
0.576

w% 0.32 gm / 100ml NaCl

NaCl equivalent method-2

NaCl equivalent E
Amount of NaCl that is equivalent to(i.e., has the
same osmotic effect (same f.p.d) as ) 1 gm of drug

1st calculate E NaCl

2nd add NaCl to reach 0.9%

?How to calculate ENaCl

Tf L.c
Tf drug Liso x
Liso ( drug ) x

wt.drug
M.wt

drug

xV

Tf NaCl Liso (NaCl) x

drug

wt.drug
M.wt

drug

xV

Liso ( NaCl ) x

drug

wt.drug 1gm

wt.NaCl
M.wt NaCl x V NaCl

wt .NaCl
M.wt NaCl x V

wt.NaCl E NaCl

M.wt

NaCl

NaCl

58.45

Liso ( NaCL ) 3.4

E NaCl

17 Liso (drug)
M.wt

drug

How to calculate amount of NaCl

w% 0.9 ( drug% E NaCl )
w% weight of NaCl in gm per 100 ml (to make solution isotonic)
drug% weight of drug in gm per 100 ml
E NaCl NaCl equivalent weight to 1gm of drug
0.9 isotonic solution of NaCl

Example I
Calculate ENaCl of drug (M.wt=187, Liso=3.4)?
E NaCl

17 Liso (drug)
M.wt

drug

E NaCl 0.31gm

How much NaCl needed to make 2% of this drug

isotonic?
0.31gm( NaCl ) 1gm(drug )
0.9 0.62 0.28 gm( NaCl )

0.62 gm( NaCl ) 2 gm(drug )

Example II
Calculate amount of NaCl needed to adjust 1.5%
Atropine SO4 (ENaCl =0.12gm)
=0.9 (W x E)
= 0.9 (1.5x 0.12)
= 0.72 gm of NaCl should be added

White Vincent method-3

Principle:
1st Addition of H2O to drug to make it isotonic
2nd addition of isotonic vehicle to bring solution to
final volume

?How to calculate amount of H2O

Suppose preparing 30ml of 1% drug isotonic
with body fluid(ENaCl =0.16gm)
1gm
100ml
?
30ml
=0.3gm
Amount of NaCl eq. to 0.3 drug
= 0.3 x 0.16 =0.048gm
0.9 gm
100 ml
0.048 gm
? ml
=5.3 ml

One step equation

v w E NaCl 111 .1
V : volume of H2O
W: weight of drug
111.1= 100/0.9

Last example

v 0.3 0.16 111 .1

v 5.3ml

II example
Add volume of H2O and then complete with
isotonic solution
Phenacaine HCl
0.06 gm (E NaCl=0.16)
Boric acid
0.3 gm (E NaCl=0.5)
sterile distilled H2O up to 100 ml

V = 111.1 x(weight x ENaCl)

V =111.1 x [(0.06x0.16)+(0.3x0.5)] = 17.7 ml H2O