Injections II

• Tonicity

  There are two ways of measuring tonicity:
• Haemolytic method

  1. The effect of various solutions of the drug is observed on the appearance of red blood cells suspended in the solutions

  2. A hypotonic solution liberates oxyhaemoglobin in direct proportion to the number of haemolysed cells

  3. The van't Hoff i factor can then be quantified
• Any method used in the determination of colligative properties

  E.g. freezing point lowering method
• 0.52°C is the freezing point of both human blood and lacrimal fluid, which corresponds to the freezing point of a 0.90% NaCl solution, which is therefore considered to be isotonic with both blood and lacrimal fluid
• Depression of Freezing Point

  • The presence of solutes in water will increase osmolarity and depress the freezing point of water
  • These effects are dependent on the concentration of solute particles
  • The freezing point of a solution can be used as a measure of its osmolarity
• The freezing point of blood serum/plasma and tears is 0.52°C, therefore an aqueous solution that freezes at 0.52°C is isotonic
• For high concentrations of electrolytes, there may be a slight deviation in the direct relationship between concentration and freezing point depression, but in most cases, the relationship holds true
• Normal freezing point

  The temperature at which solid and liquid phases are in equilibrium at 1 atm pressure
• When a solute is present

  • The vapour pressure of the solvent is lowered below that of solvent only (directly proportional)
  • Temperature must drop to re-establish the equilibrium
• Freezing point depression

  Proportional to the concentration of the solute
• Concentration

  Usually expressed in molality (i.e. moles of solute/Kg of solvent)
• Kf

  Molal depression (or cryoscopic) constant
• m

  Molality (mol/kg)
• i

  Factor to bring colligative properties of electrolytes into line with experimental results
• M

  Concentration (or c)
• L

  Value established for a number of drugs and for solutions which are isotonic with the blood
• Lisoton

  Value for a 0.90% (0.154M) solution of NaCl, which has a freezing point depression of 0.52°C and is thus isotonic with body fluids
• In diluted solutions, the interionic attraction is roughly the same for all uni-valent electrolytes 3.4
• Calculating Tonicity

  Consists in calculating the amount of NaCl that is equivalent to (i.e. has the same osmotic effect as) 1g of the drug
• Adjusting Tonicity and pH

  1. NaCl or some other substance is added to the solution of the drug to lower the freezing point of the solution to 0.52°C and make it isotonic

  2. Water is added to the drug in a sufficient amount to form an isotonic solution, then the preparation is brought to its final volume with an isotonic solution