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Once the isotonicity of a solution is determined, adjustments may be necessary.
Methods of Adjusting Isotonicity are categorized into Class I and Class II.
A) Class I Methods
Definition
Methods that involve adding solutes to adjust the isotonicity of a solution without changing its volume significantly.
Techniques
1) Sodium Chloride Equivalent Method
Concept: Calculates the amount of sodium chloride (or equivalent solute) needed to make the solution isotonic.
Sodium Chloride Equivalent (EEE): Represents the amount of NaCl that has the same osmotic effect as 1 gram of the drug.
Formula:
Steps:
Calculate the total amount of NaCl required for isotonicity.
Subtract the NaCl equivalent of the drug already present.
Add the difference as NaCl or another suitable solute.
2) White-Vincent Method
Concept: Calculates the volume of isotonic solution that can be prepared with the drug.
Formula: V = w × E × 111.1
V = Volume of isotonic solution that can be prepared.
w = Weight of the drug in grams.
E = Sodium chloride equivalent.
Adjustment:
Dilute the drug to the calculated volume with water.
Add isotonic diluent to reach the final desired volume.
Advantages
Precision: Allows accurate calculation of solute additions.
Simplicity: Straightforward calculations using known equivalents.
Limitations
Dependent on Accurate EEE Values: Requires precise sodium chloride equivalents for drugs.
Not Suitable for All Solutes: Limited to substances with known EEE values.
B) Class II Methods
Definition
Methods that involve adding water to adjust the isotonicity, followed by bringing the solution to final volume with an isotonic or buffering solution.
Techniques
1) Freezing Point Depression Method
Concept: Adjusts the solution based on its freezing point depression to match that of body fluids.
Steps:
Calculate the total freezing point depression required (−0.52°C-0.52°C−0.52°C).
Determine the freezing point depression contributed by the drug.
Add water to reach the desired freezing point depression.
Bring to final volume with isotonic diluent.
2) Sprowls Method
Concept: Similar to the freezing point method but uses tables correlating freezing point depression with volumes.
Procedure:
Use standard tables to find the volume of isotonic solution corresponding to the amount of drug.
Adjust the solution accordingly.
Advantages
Flexibility: Useful when adding solutes is impractical.
Applicability: Suitable for drugs where EEE values are not available.
Limitations
Complexity: Requires knowledge of freezing point depression contributions.
Equipment: May need instruments to measure freezing points accurately.
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