What is Distribution Law in Pharmaceutical Analysis?

Nernst (1891) investigated the distribution of numerous solutes between several solvent pairings. He made a generalisation that determines the solute distribution between two non-miscible liquids. It was called Nernst’s applications of distribution law in pharmaceutical analysis (or Nernst Partition Law), or simply Distribution Law in pharmacy or Partition Law.

When two non-miscible solvents are mixed together, a solute becomes concentrated in both solvents. C1/C2 = S1/S2, where S1 and S2 stand for the solute’s solubilities in the two solvents, symbolises solubility distribution law. It is possible to determine the solute’s solubility in the second solvent by comprehending the significance of the Distribution Coefficient (KD) and solubility in the first solvent.

Before heading to the distribution and its limitations, let’s look at its applications. 

Applications of the Distribution Law

Here are the applications of distribution law in pharmaceutical analysis. 

1. Chemical Industry

In the chemical industry, solvent extraction entails removing organic substances from aqueous solutions. Aqueous solutions are usually shaken first using organic solvents like ether or benzene. A significant portion of the organic substance flows to the ethereal since the distribution ratio favours ether. The ethereal layer is used to distil the component of the organic substance. The organic material is still there.

2. Partition chromatography

To create a paste, this mixture is spread out over a bed of wet silica. Hexane, yet another incompatible solvent, is permitted to pass through the column. The stationary liquid phase (water) comes before the mobile phase because each component of the combination is divided into separate stationary and mobile phases (hexane). Hexane is used to carefully recover the component distribution coefficients once they have been organised.

3. Desilverisation of lead (Parke’s process)  

It is one of the important applications of distribution law in pharmaceutical analysis where Zinc and lead form immiscible layers in the midst of molten argentiferous lead or zinc, spreading the silver between them. The majority of the silver accumulates into the zinc layer at 800°C because the zinc distribution ratio is approximately 300 to 1. The majority of the silver distributes evenly throughout the layer of zinc when silver is subjected to 800°C because the zinc distribution ratio is approximately 300 to 1. The alloy AgZn is produced when zinc is sprayed over silver in a retort. Silver is unaffected when zinc does not pass through. By heating it with molten zinc, the silver is extracted as much as feasible.

4. Confirmatory test 

The salt solution is treated using chlorine water. Iodine and bromine are consequently released. To get rid of the bromine or iodine, shake the mixture with chloroform.

5. Establishing a connection

Two molecules are connected in the solvents A and B (polymerised). The ensuing interactions between molecules are controlled by the distribution law.

n√Ca/Cb is equal to K,

Where, n molecules come together to form a specific molecule.

6. Determination of dissociation

In the ether, substance X exists as single molecules after being dissociated in an aqueous solution.

A distribution law can be proven to exist if x is the degree of dissociation (or ionisation). 

C1 / C2 (x-1) is equal to K,

Where,

A benzene molecule with C1 = X.

C2 is content in the aqueous layer

Conductivity data can be used to calculate x, but C1 and C2 must be estimated first. With the conductivity data, we can now calculate K. This K value can be used to find the value of x for any other X concentration.

7. Solubility determination

Let’s assume that the identification of iodine will be determined by its solubility in benzene. The distribution coefficient is derived using the equilibrium concentrations of iodine in benzene (Cb) and water (Cw) determined experimentally.

Real-life applications

• Pharmaceutical solubility in a mixture of solvents and water can be predicted.
• Drug-drug connections can be determined using the Structure-Activity Relationship (SAR).
• From a solution comprising numerous compounds, one component can be extracted.
• Preservation of emulsions and creams.

Limitations of distribution law

The following are the limitations of distribution law in pharmacy.

1. Consistent temperature – This is one of the biggest distribution law and its limitations wherein experiment generally takes place at a set temperature.

2. Stability in Molecular State- Experiments at consistent temperatures keep the molecular state stable. The solute must maintain a stable molecular state while in contact with the solvent. There must be no dissociation or solvent involvement of the solute. 
3. Dilute solutions – As a result, the solute concentrations in the two solvents are low. This law does not apply above a specific concentration. The distributed solute must not hastily react to the solvent.

Conclusion

So, that’s a wrap to the applications of distribution law in pharmaceutical analysis and the distribution law and its limitations!

When two immiscible solvents A and B are mixed in a beaker, they split into two layers. When a soluble solute X is added, it is dispersed or partitioned between the two solvents. X molecules flow from solvent A to solvent B and vice versa. After that, a dynamic equilibrium is established. The rate at which molecules of X flow from one solvent to the other is balanced at equilibrium. The distribution law imposes constraints such as constant temperature, similar chemical states, equilibrium concentrations, dilute solutions, and the non-miscibility of solvents.