Isotonic calculations

Osmosis
If a semi-permeable membrane (one that is
permeable only to solvent molecules) is used to
separate solutions of different solute
concentrations, a phenomenon known
as osmosis occurs in which solvent molecules
cross the membrane from lower to higher
concentration to establish a concentration
equilibrium. The pressure driving this movement
is called osmotic pressure and is governed by the
number of "particles" of solute in solution.
Isotonic and Iso-osmotic solutions
Solutions containing the same concentration
of particles and thus exerting equal osmotic
pressures are called iso-osmotic. A 0.9%
solution of NaCl (Normal Saline) is iso-osmotic
with blood and tears.
 Isotonic and Iso-osmotic solutions
The term isotonic, meaning equal tone, is sometimes used
interchangeably with the term iso-osmotic. The distinction
between these terms comes with the realization that red
blood cell membranes are not perfect semi-permeable
membranes, but allow passage of some solutes, such as
alcohol, boric acid, ammonium chloride, glycerin, ascorbic
acid, and lactic acid. Hence, a 2% solution of boric acid
while physically measured to be iso-osmotic (containing
same number of particles) with blood, will not be isotonic
(exerting equal pressure or tone) with blood but is isotonic
with tears.
Practically this differentiation is rarely of significance and
iso-tonicity values calculated on the basis of the number of
particles in solution is usually sufficient.
 Hypertonic and Hypertonic solutions
The clinical significance of all this is to insure
that isotonic or iso-osmotic solutions do not
damage tissue or produce pain when
administered. Solutions which contain fewer
particles and exert a lower osmotic pressure
than 0.9% saline are called hypotonic and
those exerting higher osmotic pressures are
referred to as hypertonic.
 Hypertonic and Hypertonic solutions
Administration of a hypotonic solution
produces painful swelling of tissues as water
passes from the administration site into the
tissues or blood cells. Hypertonic solutions
produce shrinking of tissues as water is pulled
from the biological cells in an attempt to
dilute the hypertonic solution.
 Hypertonic and Hypertonic solutions
The effects of administering a hypotonic
solution are generally more severe than with
hypertonic solutions, since ruptured cells can
never be repaired. The eye can tolerate a
range of tonicities as low as 0.6% and as high
as 1.8% sodium chloride solution.
 Calculation for tonicity
Several methods are used to adjust iso-
tonicity of pharmaceutical solutions. One of
the most widely used method is the sodium
chloride equivalent method. The NaCl
equivalent (E) is the amount of NaCl which has
the same osmotic effect (based on number of
particles) as 1 gm of the drug.
 CALCULATION OF DISSOCIATION (i)
FACTOR
Since osmotic pressure depends upon the number of particles
of solute(s) in solution, the osmotic pressure of an electrolyte
is directly proportional to the degree (or extent) of
dissociation.
The dissociation factor, symbolized by the letter i, can be
calculated by dividing the total number of particles (which
include undissociated molecules and ions) in a solution by the
number of particles before dissociation, i.e.,
CALCULATION OF DISSOCIATION (i)
FACTOR
 CALCULATION OF DISSOCIATION (i)
FACTOR
What is the dissociation factor of NaCl, having 80%
dissociation in water?
Assume that we have 100 particles of NaCl prior to
dissociation. Upon
80% dissociation, 100 molecules of sodium chloride yield:
 CALCULATION OF DISSOCIATION (i)
FACTOR
What is the dissociation factor of zinc chloride, having 80%
dissociation in water?
Assume that we have 100 particles of zinc chloride prior to
dissociation.
Upon 80% dissociation, 100 molecules of zinc chloride yield:
 CALCULATION OF DISSOCIATION (i)
FACTOR
SODIUM CHLORIDE EQUIVALENTS OF DRUG SUBSTANCES
The sodium chloride equivalent of a chemical is defined as the amount of
sodium chloride (in grams or grains) that has the same osmotic pressure
as that of 1 g of the chemical.
The sodium chloride equivalents are symbolized by the letter E.
The quantities of two substances that are isotonic equivalents are
proportional to the molecular weight of each multiplied by the Ivalue of
the other.
Thus, if the molecular weight and Ivalue of a given chemical are known,
one can calculate the sodium chloride equivalent, E, of that chemical as
follows:
SODIUM CHLORIDE EQUIVALENTS OF
DRUG SUBSTANCES
 SODIUM CHLORIDE EQUIVALENTS OF
DRUG SUBSTANCES
Calculate the sodium chloride equivalent of a
1% solution of pilocarpine nitrate.
Pilocarpine nitrate has a molecular weight of
271 and I of 1.8.
 SODIUM CHLORIDE EQUIVALENTS OF
DRUG SUBSTANCES
Calculate the sodium chloride equivalent of a 1% boric acid.
Boric acid has a molecular weight of 62 and i of 1.
 Calculation NaCl equivalent method
sample calculation: Calculate the amount of
NaCl required to make the following
ophthalmic solution isotonic.
Rx

Atropine Sulfate 2%
NaCl qs
Aqua. dist. q.s. ad. 30 ml
M.ft. isotonic solution
 Calculation
Step1. Determine the amount of NaCl to make 30 ml of an
isotonic solution
0.9g/100 = x/30 ml, X=0.9x30/100=0.27g
Step2. Calculate the contribution of atropine sulfate to the NaCl
equivalent
30mlx2g/100=0.6 g of atropine sulfate
NaCl equivalent of atropine (E)= 0.13
0.6x 0.13=0.078 g
Step3. Determine the amount of NaCl to add to make the
solution isotonic by subtracting (2) from (1)
0.27g-0.078g=0.192 g or 192mg.
 Calculation freezing point depression
A hypotonic solution can be made isotonic by adding
an adjusting substance, usually sodium chloride; the
exact amount of this substance to add is to be
calculated. The basic formula used to do this is
W = 0.52 a
b
where W=Weight of the added substance (g/100ml);
a=Freezing point depression of the unadjusted
hypotonic solution;
b=Freezing point depression of a 1% w/v solution of
the adjusting substance.
 Calculation freezing point depression
The 0.52 in the top line of the fraction is
measured in C so the term a must also be
measured in C
Reference texts such as The Pharmaceutical
Codex usually quote freezing point depression
values for one particular concentration of a
pharmaceutical preparation, usually 1% w/v. If
the isotonic solution being prepared has a
different concentration say 2% w/v then the
value of b must adjusted accordingly
 Example
The freezing point depression of a 1% w/v
solution of morphine sulfate is 0.08C and that
of 1% w/v sodium chloride solution is 0.576.
How many grams each of morphine sulfate
and sodium chloride are required to prepare
50ml of a 1% w/v morphine sulfate solution
isotonic with blood plasma?
 Solution
The freezing point of (a 1% w/v solution of)
morphine sulfate is 0.08C.
The required freezing point is 0.52C,
therefore the freezing point must be lowered
by: 0.52C - 0.08C = 0.44C.
A 1% w/v sodium chloride solution produces a
freezing point depression of 0.576C, therefore
the weight of sodium chloride required to
produce a depression of 0.44C is:
 Solution
W = 0.52 a/ b
= 0.52 0.08 0.576 = 0.7638g/100ml
The quantities needed to make a 50ml solution
will be:
1. Morphine sulfate: (1g/100ml) x 50ml = 0.5g
2. Sodium chloride: (0.7638g/100ml) x 50ml =
0.3819g
 Example
A pharmacist receives a prescription for 10ml
of isotonic 0.5% w/v chloramphenicol eye
drops, what weight of sodium chloride is
required to make the solution isotonic with
tears?
 Solution
From The Pharmaceutical Codex a 1% w/v solution of
chloramphenicol has a freezing point depression of
0.06C.
Therefore a 0.5% w/v solution has a freezing point
depression of 0.06C 0.5 = 0.03C.
The required freezing point is 0.52C, therefore the
freezing point must be lowered by: 0.52C0.03C =
0.49C.
1% w/v sodium chloride produces a freezing point
depression of 0.576C, therefore the weight of sodium
chloride required to produce a depression of 0.49C is:
 Solution
W = 0.52 a/ b = 0.52 0.03 0.576 =
0.8507g/100ml
As the prescription requests 10ml of eye drops
we require (0.8507 10)/100 = 0.08507g =
85.07mg of sodium chloride.
 The sodium chloride equivalent method is the
most frequently used method in the
calculation of the amount of sodium chloride
needed to prepare isotonic drug solutions.
The sodium chloride equivalent of any drug
substance, as discussed earlier, is the amount
(in grams) of sodium chloride that is
osmoticallyequivalent to 1 g of the drug.
 ISOTONICITY ADJUSTMENTS BY
CRYOSCOPIC METHOD
The freezing point depression (or lowering) of a solvent is dependent only
on the number of particles in the solution. Blood plasma has a freezing
point of 0.52 {or freezing point depression of 0.52, i.e., ( [0.52])}.

If freezing point depression value of a chemical in certain concentration is

known, one can calculate the concentration of that chemical required for
isotonicity by setting a proportion as follows:
 Thus, 0.9% sodium chloride has the same
osmotic pressure and the same freezing point
depression of 0.52 as that of blood plasma,
red blood cells, and tears.
Drug solutions which have a freezing point
depression of 0.52 are, therefore, isotonic
with blood.
 Step 1:Find the value of freezing point depression of the
drug at 1% concentration,.

Step 2:Subtract _T1% f of the drug from the value of

freezing point. depression of 0.9% sodium chloride solution,
i.e., 0.52. This difference may be symbolized as _Tf, which is
the freezing point lowering needed for isotonicity.

Step 3:Since 0.9% sodium chloride has a freezing point

depression of 0.52, one can calculate the percentage
concentration of sodium chloride required to lower the
difference in freezing points, i.e., the value obtained.
 Example
Compound the following prescription.

Rx
Atropine Sulphate 1%
Sodium chloride Q.S
Purified up to 100ml
Make isotonic solution for ophthalmic use
 Step 1:Freezing point depression (_Tf) of 1% atropine
solution is 0.07.
Step 2:Find _Tf by subtracting the _Tf value of 1%
atropine sulfate
from the _Tf of blood plasma, i.e.,
0.52 0.07 = 0.45. This means,
sufficient sodium chloride must be added to lower the
freezing point by an additional 0.45.
Step 3:Find the percentage concentration of sodium
chloride required by setting up the proportion as
follows:
It is observed that 1% solution of sodium chloride has a freezing point lowering of 0.58.
Therefore, one can also express the proportion as:

Answer: solving for X, we get: (0.45/0.58) 1 = 0.78%

 ALLIGATION

Alligation is a method of solving

problems that involves the
mixing of solutions or
substances with different
percentage strengths
Alligation alternate is a method
to calculate the number of parts
of two or more components of
different strengths mixed to
prepare a desired strength.

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 EXAMPLE
ALLIGATION
What is the percentage of zinc oxide in an ointment prepared
by mixing 200 grams of a 10% ointment, 50 grams of a 20%
ointment, and 100 grams of a 5% ointment

0.10 x 200 g = 20 grams

0.20 x 50 g = 10 grams
0.05 x 100 g = 5 grams
350 g 35 grams

35 grams 350 grams = 0.10 x 100% = 10%

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 EXAMPLE
ALLIGATION ALTERNATE
A pharmacist needs to prepare 50 mL of 3% hydrogen peroxide
solution. He has 30% and 1.5% solutions in stock. How many
mL of each should he use?
AC=Y
Percent Percent Proportions
Available Desired required CB=X
A X
X and Y are
C proportions of A and B
(respectively) needed
B Y for the entire
preparation
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 EXAMPLE
ALLIGATION ALTERNATE
A pharmacist needs to prepare 50 mL of 3% hydrogen peroxide
solution. He has 30% and 1.5% solutions in stock. How many
mL of each should he use?

Percent Percent Proportions

Available Desired required 1.5 parts of 30%
30% 1.5
27 parts of 1.5%
3%
Total Parts: 28.5
1.5% 27

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 EXAMPLE
ALLIGATION ALTERNATE
A pharmacist needs to prepare 50 mL of 3% hydrogen peroxide
solution. He has 30% and 1.5% solutions in stock. How many
mL of each should he use?

We need 1.5 of all 28.5 parts to contain 30%

Hydrogen peroxide
1.5/28.5 = x/50mL
X = 2.63mL of 30%
We need 27 parts of all 28.5 parts to contain 3%
Hydrogen peroxide
27/28.5 = x/50mL
X = 47.37mL of 1.5%
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 CALCIUM-ALBUMIN
Almost 50% of calcium is bound to plasma
proteins
If levels of proteins are low, then the serum
calcium may be inaccurate
If albumin is low, calcium will appear to be low,
when it levels are actually within normal limits
Correct levels when Albumin is less than 4 g/dL
Corrected Ca2+ = Ca2+ + 0.8 [4 albumin(g/dL)]

43
 SODIUM-GLUCOSE

In patients with hyperglycemia, glucose does not

enter the cell, causing a shift of fluid from
intracellular to extracellular
The shift of fluid dilutes the concentration of
sodium in the extracellular fluid
This type of hyponatremia (translational) does
not need to be treated, instead control of glucose
levels is indicated
Corrected Na+ = Na+ + 0.016(Serum Glucose
100)

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Important Calculation Concepts

INFUSION FLOW RATES

45
 EXAMPLE

A physician orders 2 liters of D5W to be administered over 8

hours. The IV administration set in your pharmacy delivers 10
drops/mL. How many drops per minute should the patient be
set to receive?

2 Liters/ 1000mL/ 1 hour/ 10 drops/ 42 drops/

8hours 1 Liter 60 min 1mL min

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