Methods of Adjusting Isotonicity

• Once the isotonicity of a solution is determined, adjustments may be necessary.
• Methods are categorized into Class I and Class II.

1.Class I Methods of Adjusting Isotonicity

• Definition

  • Methods that involve adding solutes to adjust the isotonicity of a solution without changing its volume significantly.

• Techniques

  • 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:

    • Amount of NaCl needed = (0.9

    • 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.

  • 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.

2.Class II Methods of Adjusting Isotonicity

• 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

  • 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.

  • 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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