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Parenterals and Ophthalmic Preparations

Isotonic Solutions
• Definitions

1. Isotonic Solution: is a solution having the same osmotic pressure as a body

fluid. Ophthalmic, nasal, and parenteral solutions should be isotonic.
2. Hypotonic solution: is a solution of lower osmotic pressure than that of a body
fluid. These solutions lead to swelling and bursting of RBCs, which in turn
leads to hymolysis.
3. Hypertonic solution: is a solution having a higher osmotic pressure than that
of a body fluid. These solutions lead to shrinkage of the RBCs.
Isotonic solutions Calculations
I. Procedure for Calculation of Isotonic Solutions Using Sodium Chloride
a. Calculate amount in grams of NaCl represented by the ingredients in

prescription. Multiply the amount in grams of each substance by its NaCl

equivalent “either from tables or by calculation”.

b. Calculate amount in grams of NaCl, alone, that would be contained in an

isotonic solution of the total volume specified in prescription.

i.e. 0.9 Æ 100 because 0.9% solution of NaCl is isotonic.

X Æ total of the prescription.

c. Subtract the amount of NaCl represented by the ingredients in the prescription

(step#1) from the amount of NaCl needed to prepare isotonic solution (step#2)

i.e. step # 2 – step # 1.

d. If an agent other than sodium chloride such as boric acid, dextrose, sodium or

potassium nitrate is to be used to make a solution isotonic, divide the amount

of NaCl (step 3) by NaCl equivalent of the substance used to adjust Isotonicity

NaCl from step # 3

i.e. .
E − value

Calculation of Sodium Chloride equivalent of a substance (if it is not tabulated):

M.Wt of NaCl i factor of substance

Sodium Chloride equivalent = *
i factor of NaCl M.Wt of substance

Problems on calculating the dissociation factor (i) of an electrolyte:

1. Zinc Sulfate ZnSO4 is a 2-ion electrolyte, dissociation 40% in a certain

concentration. Calculate its dissociation factor.

2. Zinc Chloride (ZnCl2) is a 3-ion electrolyte; dissociation 80% in a certain

concentration, calculate (i).

In general, we may use the following tabulated values in case of solutions of 80% or
higher concentrations:
Nonelectrolytes, slightly dissociated subs. 1
Substances that dissociate into two ions 1.8
Substances that dissociate into three ions 2.6
Substances that dissociate into four ions 3.4
Substances that dissociate into five ions 4.2

Problem on calculating the E-value of a substance:

Papavarine HCl (mwt = 376) is a 2-ion electrolyte dissociating 80%. Calculate its
E-value (Sodium Chloride equivalent), where its dissociation factor (i) = 1.8
Problems on isotonic solutions calculations using the NaCl E-value:

1. How many grams of NaCl should be used in compounding the following

Pilocarpine nitrate 0.3 g E =0.23
Sod. Chloride Q.S.
Purified water ad 30 ml
Make isotonic solution.

2. Oxytetracyline HCl 0.5% E = 0.12
Tetracaine HCl 2% solution 15 ml
Sodium Chloride Q.S.
Purified water ad 30 ml
Make isotonic solution
2% solution of Tetracaine HCl is isotonic. How many mls of 0.9% solution of
Sodium Chloride should be used?

3. Tetracaine HCl 0.5% E(0.18)

Epinephrine bitartarate 1:1000 solution 10 ml
Boric acid Q.S E(0.52)
Purified water ad 30
Make isotonic solution
The solution of Epinephrine bitartarate (1:1000) is already isotonic. How many
grams of boric acid should be used in compounding the prescription?

II. Isotonic Solutions Calculations using Freezing Point Data:

The calculations involved in preparing isotonic solutions may be made in terms of
data relating to the colligative properties “freezing point depression, osmotic pressure,
elevation of boiling point” of solutions. A comparison of freezing points for example
may be used for this purpose.

1. How many mg each of NaCl and dibucaine HCl are required to prepare 30 ml of a
1% solution of dibucaine HCl isotonic with tears?
From tables:
1% NaCl Tf = 0.58
1% Dibucaine HCl Tf = 0.08
Freezing point of blood and lachrymal fluid is – 0.52 oC.

2. How many grams of NaCl should be used in compounding the following

Naphazoline Hcl 1%
NaCl Q.S.
Purified water ad 30ml
Make isotonic solution. Use the freezing point depression method.

Tf blood = 0.52
Tf 1% NaCl = 0.58
Tf 1% Naphazoline HCl = 0.16

III. Isotonic Solutions Calculations using White-Vincent Method:

Computing tonicity involves the addition of water to a specified amount of drug
to make isotonic solution, followed by the addition of an isotonic buffered diluting
vehicle to bring the solution to the final volume.

V = W * E * 111.1
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.

Make the following solution isotonic with respect to membrane. Provided that you have
isotonic diluting solution:
Phenacaine HCl 0.06 g (E 0.2)
Boric acid 0.3 g (E 0.52)
Sterilized water to 100 ml