Pharmaceutics IIB

Part II
Tutorial 6
Dr. Muna Najm
mnajm@sharjah.ac.ae
Adjunct Faculty – Lecturer
Department of Pharmaceutics & Pharmaceutical Technology

Spring 2024
Calculations for Isotonicity
Tutorial 6
Isotonic Solutions

 Dextrose, sorbitol, mannitol and NaCl are usually used to adjust

isotonicity of parenteral preparations
 In order to prepare ophthalmic or parenteral products, many methods of
calculations may be used to determine the isotonicity of the solution:

Freezing point depression method

NaCl equivalent method
White-Vincent method
Freezing Point Depression Method
Important Facts
• Body fluid has a FP depression of 0.52 i.e body fluid freezes @ -0.52 oC
(F.P of pure water is 0 oC)
• Therefore any solution TO BE ISOTONIC should have FP depression of
0.52
• 1 mole of any substance in 1000 gm of water will have a FP depression of
1.86
• For electrolytes, this value is multiplied by i (1.86 x i)
• Hypotonic solutions have a freezing point depression higher than -0.52 oC
and require the addition of a solute to depress the freezing point to -0.52 oC.
Freezing Point Depression Method
• For an electrolyte; the dissociation factor “i” must be included in the
proportion
• According to the # of ions produced after dissociation “i” may have the
following values:

• Non-electrolytes and substances of slight dissociation 1.0

• Substances that dissociates into 2 ions (e.g. NaCl) 1.8
• Substances that dissociates into 3 ions (e.g. CaCl2) 2.6
• Substances that dissociates into 4 ions (e.g. Na3PO4) 3.4
FPD Method

Preparation of isotonic solution of non-electrolyte: When 1 mole of any non-

electrolyte, that is a substance with negligible dissociation such as boric acid is
dissolved in 1000 g of water, the freezing point of the solution is about 1.86°C below
the freezing point of pure water.
By simple proportion, therefore, we may calculate the weight of any nonelectrolyte that
should be dissolved in each 1000 g of water if the solution is to be isotonic with the
body fluids

Example 1: Prepare an isotonic solution of non-electrolytes e.g. Boric acid

M Wt = 61.8 gm
Freezing Point Depression Method
Example 1: Prepare an isotonic solution of non-electrolytes e.g. Boric acid , M Wt
= 61.8 gm

Solution: To make an isotonic solution of boric acid

1mole = 61.8 gm 1.86 oC
X 0.52 oC
• X = 17.3 gm
• Or, 17.3 gm of boric acid in 1000 gm of water (approximate strength of 1.73%)
should make a solution isotonic with body fluids.
FPD Method
Preparation of isotonic solution of electrolyte:
 Since osmotic pressure depends on the number of particles, substances that dissociate
have a tonic effect that increases with the degree of dissociation and the greater the
dissociation, the smaller the quantity required to produce any given osmotic pressure.
 If we assume that sodium chloride in weak solutions is about 80% dissociated, then
each 100 molecules yield 180 particles, or 1.8 times as many particles as are yielded by
100 molecules of a non- electrolyte.
 This dissociation factor, commonly symbolized by the letter i, must be included in the
proportion isotonic solution of sodium chloride (molecular weight, 58.5) is calculated as:
 1 mole = 58.5 g NaCl → produce freezing point depression of 1.86°C x 1.8 (i)
Preparation of isotonic solution of electrolyte:

According to the # of ions produced after dissociation “i” may have the
following values:

Non-electrolytes and substances of slight dissociation 1.0

Substances that dissociates into 2 ions (e.g. NaCl) 1.8
Substances that dissociates into 3 ions (e.g. CaCl 2) 2.6
Substances that dissociates into 4 ions (e.g. Na 3PO4) 3.4
Freezing Point Depression Method
Example 2: Prepare an isotonic solution for electrolytes e.g. NaCl (M Wt = 58.5)

Solution 1 mole = 58.5 gm 1.86 oC x 1.8

X 0.52 oC

• X = 9.09 gm
• Or, 9.09 gm of NaCl in 1000 gm of water (approximate strength of 0.9% w/v)
should make a solution isotonic with body fluids.
FPD Method – How much of NaCl as an isotonicity adjuster is required?

Steps

1. We find out the freezing point depression caused by the given amount of the drug in the
prescription in the given volume of water.

(∆Tf1% = 1% solution of drug “include DF”)

2. Find Required FPD - We subtract Step 1 answer from 0.52 (FPD of body fluids).

FPD Required = FPD body fluids – FPD of drug

3. For the remaining depression in freezing point, we add sufficient sodium chloride, knowing that
1% sodium chloride has a freezing point lowering of 0.58°C.
Example3: How much NaCl is required to render 100 ml of 1% solution of apomorphine
hydrochloride isotonic with blood serum?
FPD caused by adding 1 gm of drug in 100 mL of water
(∆Tf1% = 1% solution of drug “include DF”)
Freezing Point Depression Method
Example3: How much NaCl is required to render 100 ml of 1% solution of
apomorphine hydrochloride isotonic with blood serum?

Solution:
• From the table, 1% solution of apomorphine hydrochloride has FPD = 0.08
• Therefore we need an additional amount of NaCl with a FPD = 0.44 (0.52-
0.08) to make the solution iosotonic.
• From the table
1% NaCl 0.58 oC
X 0.44 oC
• X= 0.76%
• Thus an isotonic solution can be obtained by dissolving 1 gm of apomorphine
hydrochloride + 0.76 gm of NaCl in 100 ml of solution.
NaCl equivalent method
• The NaCl equivalent: is the amount of a NaCl that has the same osmotic effect as 1 gm
of the drug

• Steps:
1. Quantity of D’ (consider amount in given volume of preparation) x NaCl
equivalent
2. Calculate the amount of NaCl that makes an isotonic solution (always 0.9% w/v) -
(consider amount in given volume of preparation)
3.- = amount of NaCl that must be added
4. If another inert substance such as dextrose is used to adjust the isotonicity, the
value obtained from step 3 is converted to the amount of inert substance using its
NaCl equivalent (E ”1 g of drug” - from table)
NaCl equivalent method
Example 4: A solution contains 1 gm ephedrine sulphate in volume of 100 ml. What quantities
of NaCl must be added to make the solution isotonic? How much dextrose would be required
for this purpose?

Solution:
STEP 1: 1 x 0.23 = 0.23 g of NaCl
STEPS 2, 3: An isotonic solution of NaCl solution contains 0.9 gm of NaCl in 100 ml solution
0.9 - 0.23 = 0.67 g of NaCl must be added
STEP 4: If dextrose should be used instead of NaCl, get the NaCl equivalent value for
dextrose from the table (= 0.16)
1gm dextrose 0.16 gm NaCl
X 0.67 gm NaCl
• X= 4.2 gm of dextrose should be added to make the solution isotonic.
 NaCl Equivalent
1 gram of drug is equivalent to E-value
E-value can be replaced by 1 gram of drug
White-Vincent Method
Steps
• Calculate the volume of water added to the D’ to make an isotonic solution
W = Use the amount of drug
needed to prepare certain
V= (W x E ) x 111.1 volume of solution

V= [(W1 x E1) + (W2 x E2)] x 111.1

• Add isotonic solution or buffer to bring the solution to its final volume

• Where: W = grams of drug. E = sodium chloride equivalent (tabulated). V = volume

in mL of isotonic solution that may be prepared by mixing drug with water.
White-Vincent Method
Example 5: We want to prepare 30 mL of 1% solution of cocaine
hydrochloride (E= 0.16) isotonic with body fluid.
White-Vincent Method
Example 5: We want to prepare 30 mL of 1% solution of cocaine
hydrochloride (E= 0.16) isotonic with body fluid.

Solution
• Step a: V= 0.3 x 0.16 x 111.1= 5.3 mL
• Step b: to complete the volume to 30 mL enough isotonic NaCl or another
isotonic or isotonic-buffered solution should be added (30-5.3 = 24.7 ml)
 White-Vincent Method
Example 6: Make 100 ml of the following solution isotonic with lacrymal fluid
Phenacaine hydrochloride 0.06 g E= 0.2
Boric acid 0.3 g E= 0.5
Sterilized distilled water QS
Problem 1
What proportion of procaine hydrochloride will yield a solution
isotonic with blood plasma
FPD of 1% procaine hydrochloride is 0.122
FPD of 1% NaCl is 0.58
Problem 2
Find the proportion of NaCl required to render 1.5% solution of
procaine HCl isotonic with blood plasma. FPD of 1% procaine
hydrochloride is 0.122
FPD Method – How much of NaCl as an isotonicity adjuster is required?

Steps

1. We find out the freezing point depression caused by the given amount of the drug in the
prescription in the given volume of water.

(∆Tf1% = 1% solution of drug “include DF”)

2. Find Required FPD - We subtract Step 1 answer from 0.52 (FPD of body fluids).

FPD Required = FPD body fluids – FPD of drug

3. For the remaining depression in freezing point, we add sufficient sodium chloride, knowing that
1% sodium chloride has a freezing point lowering of 0.58°C.
Example3: How much NaCl is required to render 100 ml of 1% solution of apomorphine
hydrochloride isotonic with blood serum?
Problem 3
How much boric acid should be used in compounding the following
prescription to render it isotonic with lachrymal fluid.
NaCl equivalent (E) of Boric acid = 0.5

Rx
Holocaine HCl 1% E = 0.2
Clorobutanol 0.5% E = 0.24
Distilled water ad 60 mL
Problem 4
1 fluidounce solution contains 4.5 grains of Ag nitrate. How much NaCl
must be added to this solution to make it isotonic with nasal fluid? Assume
the nasal fluid has an isotonic value of 0.9 g of NaCl/100ml (E Ag Nitrate=
0.68)
NaCl equivalent method
• The NaCl equivalent: is the amount of a NaCl that has the same osmotic effect as 1 gm
of the drug

• Steps:
1. Quantity of D’ (consider amount in given volume of preparation) x NaCl
equivalent
2. Calculate the amount of NaCl that makes an isotonic solution (always 0.9% w/v) -
(consider amount in given volume of preparation)
3.- = amount of NaCl that must be added
4. If another inert substance such as dextrose is used to adjust the isotonicity, the
value obtained from step 3 is converted to the amount of inert substance using its
NaCl equivalent (E ”1 g of drug” - from table)
Thank You