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## DISTRIBUTION LAW

When a solid is added into two non-miscible liquids, it is distributed between them in a manner similar to the distribution of a gas between a liquid and a gas phase.

Sometimes it is required to remove certain substances from and aqueous solution, which are soluble in organic solvents like ether, chloroform, or some other solvent immiscible in water. In the alkaloidal assays, it is common practice to extract organic substances by chloroform or ether from aqueous solutions. This is done by shaking the solution together with some solvent; say ether, in a separating funnel, removing the ether solution, and repeating the treatment with ether until practically all of the substance has been extracted. The substance can be recovered from the rather solution by the ether. If we were to shake the aqueous solution with ether until equilibrium was reached, and if the water and ether solutions were dilute, the distribution of the solute in the two solvents, i.e. ether and water, would follow a very simple law, known as the Distribution law or the Partition law.

If C is the molar concentration in the ether layer and C1 is the molar concentration in the water layer, then,

C/C1=K, where K is the partition coefficient

The value of K will be constant provided the solute has the same molecular weight in the two solvents.

Suppose iodine (1) is added in the mixture of water and chloroform, it will distribute in water and the chloroform according to the solubility in the solvents. Iodine is slightly soluble in water but very soluble in organic solvent. If we want to extract iodine from its aqueous solution, we will have to shake it with organic solvent like chlorofiem or carbon tetrachloride.

The ratio of the concentration of I in the two solvents at constant temperture constant, as is shown by the above expression for equilibrium. This constant is the partion coefficient or distribution coefficient. If K> I solute prefers organic solvent and if K<1 solute prefers the aqueous solvent.

Thus Distribution Law can be defined as" when a solute distributes itself between two immiscible solvents, the ratio of the concentration of the solute in the two solvents, provided its molecular weight is the same in each of them, is constant and independent of any other molecular species which may be present. If in the second solvent, the molecules are associated, n molecules associating to form an associated molecule.

## APPLICATIONS OF DISTRIBUTION LAW

The distribution law commenly called Nernst's distribution law is applicable in pharmacy in following important phenomenon:

1.﻿﻿Solubility of drugs in water and other solvnets and in mixture of solvents can be predicted.

2.﻿﻿Extraction process: The drugs from biological fluids such as blood, urine and tissues can be extracted efficiently by the principle of multiple extraction.

3.﻿﻿﻿This can be used in partition chromatography to separate organic substance from mixtures.

4.﻿﻿﻿In vivo drug absorption can be predicted by the value of partition coeffcient.

5.﻿﻿﻿Passage of drug through membranes specially to evaluate semisolids;

6.﻿﻿﻿Preservation of emulsions and creams: These biphasic systems contain two phases, Oil and aqueous phase therefore preservatives added may distribute in both the phases. The amount of preservative can be decided by determining the distribution coefficent whether < or > 1.

7.﻿﻿﻿Charcteristics of Drug molecules: The oil-water partitin coefficients can predict the hydrophilic or hydrophobic nature of the drug. This may help in structure activity relationship (SAR) study of the series of drugs.

8.﻿﻿﻿Chemical modificatin: Chemical changes related to lipid solubility and its effect on Gl absorptions are best examplified by the barbiturates.

## LIMITATIONS OF DISTRIBUTION LAW

The conditions to be satisfied for the application of the Nernst's Distribution law are

1.﻿﻿﻿Constant temperature: The temperature is kept constant throughout the experiment.

2.﻿﻿﻿Same molecular state: The molecular state of the solute is the same in the two solvents. 3.The law does not hold if there is association or dissociation of the solute in one of the solvents.

4.﻿﻿﻿Equilibrium concentrations: The concentrations of the solute are noted after the equilibrium has been established.

5.﻿﻿﻿Dilute solutions: The concentration of the solute in the two solvents is low.
6.The law does not hold when the concentrations are high.

7.﻿﻿﻿Non miscibility of solvents: The solvents are to be allowed for separation for the sufficient time.

8.﻿﻿﻿Non-miscibility of solvents: The two solvents are non-miscible or only slightly soluble in each other. The extent of mutual solubility of the solvents remains unaltered by the addition of solute to them.

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