Osmotic pressure, Osmolality and Isotonicity

Osmotic pressure is the measure of the extent to which a solution can absorb water through a differentially permeable membrane. It is expressed as Osmoles, which is the number of moles of the solute that contribute to the osmotic pressure of the solution.

Osmotic pressure can either be represented by Osmolality, which is the number of osmoles per kilogram of the solution (osml/kg), or Osmolarity, which is the number of oslmoles of solute per liter of the solution (osml/L).

A solution is rendered isotonic if the osmole concentration of the solution is same as the cells or the biological fluids.

For Ophthalmic and Parenteral preparations, it is a crucial requirement to make the preparation isotonic.

Usually, Sodium Chloride Equivalent, method is utilized to adjust the osmolality of the solution.

According to this method, a solution containing 0.9% NaCl, which has an approximately 290 mosml/kg osmolality, is considered isotonic.

As there is a need to add buffers, antioxidants, cheleating agents, preservatives etc. to stabilize the formulation, which also contribute to the osmolality of the preparation, a calculated amount of Sodium Chloride or some other salt is added to attain the osmolality that is equivalent to 0.9% NaCl solution (290 mosm/kg). The sodium chloride equivalent method allows us to calculate the quantity of sodium chloride or some other suitable salt, which is required to produce an isotonic preparation.     

Check the following example to understand the use of this method.

Example,

Calculate the quantity of Sodium chloride that is required to create an isotonic tobramycin ophthalmic solution. If we use sodium sulphate instead of sodium chloride, how much it would be used to make the solution isotonic.

Tobramycin                            3 g

Boric acid                              5 g

Sodium borate                    1.1 g

Benzalkonium chloride        0.1 g

Disodium EDTA                 0.1 g

Sodium Chloride                      ?

Purified water Q.S           500 mL

The concentration of sodium chloride that is required to make 500 mL of water isotonic, can be calculated as,

500 x 0.009 = 4.5 g

Lets multiply the quantities of other ingredients with their Sodium chloride equivalent factors.

Tobramycin                        3 g x 0.07 = 0.21 g

Boric acid                             5 g x 0.52 = 2.6 g

Sodium borate                 1.1 g x 0.36 = 0.396 g

Benzalkonium chloride  0.1 g x 0.16 = 0.016 g

Disodium EDTA                 0.1 g x 0.24 = 0.024 g

                                         Total             = 3.246 g

Now we get the concentration of sodium chloride by subtracting this value from 4.5 g.

Sodium chloride = 4.5 – 3.246 = 1.25 g

If we need to use Sodium sulphate instead of sodium chloride, we divide this value with the sodium chloride equivalent factor of Sodium sulphate.

Sodium sulphate = 1.25 / 0.58 = 2.15 g