Isotonicity

PHT 434
osmosis

• Osmosis is the diffusion of solvent through a semi-

permeable 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 of Tonicity
Hypotonic isotonic Hypertonic

NaCl 0.2% NaCl 0.9% NaCl 2%

solute
Inside
›outside
solute solute
Inside
=outside
solute solute
Inside
‹outside
solute

swelling equilibrium shrinkage

Why using isotonic solutions?
 Isotonicity & route of administration

• Subcutaneous injection:
 not necessarily “small dose” but isotonicity reduce pain.
• Hypodermoclysis
 should be isotonic “Large volume”
• Intramuscular injection
 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 & route of administration
cont.

• Intrathecal injestion
 Should be isotonic
• Eye drops
 Rapid diluted by tear, but most of it is isotonic to
decrease irritation
• Eye lotions
 Preferably isotonic
• Nasal drops
 Isotonic, but not essentially
Classes of adjustment of isotonicity

• Class I
 Adding substace to lower f.p of solution to -0.52º
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 - ΔTf

• ΔTf =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 = 0.52º

1- Freezing point depression (FPD)
“cryoscopic method”.
• F.P. of blood & tears = - 0.52º
• Any solution have F.P. = - 0.52º is isotonic.
• Any solution have F.P. › - 0.52º is hypotonic
• - 0.4º hypotonic
• -0.6º hypertonic
• Add solute to hypotonic solution to reach f.p.d
of blood (- 0.52º )
How to calculate?

0.52  a
w% 
b
= conc. gm/100 ml of adjusting substance
w%
a = f.p.d of 1% of unadjusted substance(table) X percentage strength

b = 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=0.58º, F.p.d of 1%drug=0.08º

0.52º  a 0.52º 0.08º

w%  w%  w%  0.76%
b 0.58º
• 1% drug 0.08º (0.52º- 0.08º=0.44º)
• 1% NaCl 0.58º w%  0.76%
w% NaCl 0.44º
Example II

• adjust isotonicity of procaine HCl 3% using

NaCl ? Fpd of 1%NaCl=0.57º, f.p.d of 1%
drug=0.112º
0.52  a
w% 
b
0.52  (0.112 * 3)
w% 
0.576

w%  0.32 gm / 100ml 
 NaCl
2-NaCl equivalent method

• 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
wt.drug wt.NaCl
Tf drug  Liso x Tf NaCl  Liso(NaCl) x
M.wt drug xV drug
M.wt NaCl x V NaCl

wt.drug wt.NaCl
Liso( drug) x = Liso( NaCl ) x
M.wt drug xV drug
M.wt NaCl x V NaCl

wt.drug  1gm wt.NaCl  ENaCl M.wt NaCl  58.45

Liso( NaCL )  3.4
17 Liso(drug)
E NaCl 
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)?
17 Liso(drug)
E NaCl  ENaCl  0.31gm
M.wt drug

• How much NaCl needed to make 2% of this drug

isotonic?
0.31gm( NaCl )  1gm(drug ) 0.62 gm( NaCl )  2 gm(drug )

0.9  0.62  0.28 gm( NaCl )

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
3-White – Vincent method

• 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  ENaCl 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
example II
Add volume of H2O and then complete with
isotonic solution
Phenacaine HCl 0.06 gm (ENaCl=0.16)
Boric acid 0.3 gm (ENaCl=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