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.

Methods of Adjusting Isotonicity

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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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