Page 5 - Laboratory manual for students FAR222 2019 20

FAR 222 Dosage Form II Laboratory Manual

as surface active agents. In this section we shall just consider a few aspects of the formulation:
the vehicle, adjustments to osmolarity/tonicity and the preservation of parenteral solutions.

i. The vehicle

The vehicle is a pharmacologically inert, non-toxic, non-irritant liquid in which drug is presented,
generally as a solution though occasionally as a suspension or emulsion. Water is usually the
vehicle of choice although co-solvents or a suitable oily liquid may be employed.

ii. Osmolarity/osmolality and isotonicity

Osmolarity/osmolality is a measure of the osmotic potential of a solution, ie the potential for
water to move across a semi-permeable membrane. The membranes of red blood cells
(erythrocytes) are semi-permeable. Solutions with the same osmolarity as erythrocytes are
said to be isotonic. Injections which are not isotonic may cause haemolysis of blood cells,
irritation and pain on injection.

There are a number of methods available for calculating the amount of additional substance
to be added to a drug solution to render it isotonic, including freezing point depression, the
use of sodium chloride equivalents, molar concentrations, White-Vincent method and Sprowl’s
method. The calculations covered in FAR 122 Dosage Form I is highly relevant.
The required amount of adjusting substance required to make a solution isotonic is given by
the equation:

0.52 −
=

where

w = the weight (g) of the added substance in 100 mL of the final solution (%w/v)
a = the depression of the freezing point (∆Tf 1%) produced by the medicament already present
in solution, calculated by multiplying the value for the medicament by the strength of the
solution (%w/v)

b = ∆Tf 1% of water produced by 1 %w/v of the adjusting substance

An example of osmolarity calculation is shown below using freezing point depression method.

How much anhydrous dextrose is needed to make a 150 mL of infusion containing 0.5 %w/v
sodium chloride isotonic?

From the British Pharmaceutical Codex (BPC) 1973, the freezing point depression of a 1%
solution of sodium chloride is 0.576. It means that sodium chloride depresses the freezing
point of water by 0.576°C.

Thus, freezing point depression of unadjusted solution = 0.5 × 0.576 = 0.288°C

1% solution of anhydrous dextrose depresses the freezing point of water by 0.101°C.

0.52 − 0.52 − 0.288
= = = 2.3
0.101

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