Define solubility, parameters and factors affecting solubility of drugs

Define solubility and solubility parameters. Write the factors influencing the solubility of the drug.


Solubility is the property of solid, liquid, or gaseous chemical substances called solute to dissolve in a solid, liquid, or gases solvent to form a homogeneous solution of the solute in the solvent.

The solubility of a substance fundamentally depends on the solvent used and on temperature and pressure.

The extent of the solubility of a drug in a specific solvent is measured as a saturation concentration where adding more solute does not increase its concentration in the solution.

The solubility of a given solute is the maximum concentration to which it can be dissolved in a particular solvent to yield a homogeneous monophasic system.

The solvent is commonly a liquid. It can be a pure substance or a mixture of two liquids.

The solubility of a substance in a particular solvent is defined as the concentration of a substance in a saturated solution at a certain temperature. A solution is said to be saturated when it contains the maximum amount of solute that a solvent can dissolve at a particular temperature. Temperature can affect solubility, so the temperature must be particular when the solubility of a substance has to be expressed.

Under specific conditions and unsaturated or saturated solutions can be obtained. And the unsaturated solution is one that contains the dissolved solute in a concentration less than that required for complete saturation at a particular temperature. A supersaturated solution is one that contains more concentration of solute in the dissolved state than it is available in a normal state at a definite temperature. A supersaturated solution may simply be obtained by cooling a saturated solution to a low temperature without any precipitation.

Parameters of solubility

  • Molecular attractions
  • Van der Waals force
  • The Hildebrand solubility parameter
  • Vaporization
  • Cohesive energy density

Molecular attraction

Liquid and solids differ from gases because the molecules of liquids and solids are held together by a certain amount of intermolecular forces. For a solution to occur, the solvent molecules must overcome this intermolecular binding in the solute and find their way between and around the solute molecules.

Van der Waals force

The winding forces between molecules are called Van der Waals force.

Van der Waals forces are due to electromagnetic interactions between molecules.

The Hildebrand solubility parameter

It is the total van der Waals force, which is reflected in the simplest solubility value.


When a liquid is heated to its boiling point, after that the energy added to the liquid is used for converting liquid into gas. This process of converting liquids into gases by applying heat is known as vaporization.

Cohesive energy density

The cohesive energy density of a liquid is a numerical value that indicates the energy of vaporization in calories per cubic centimeters.

Factors influencing the solubility of a drug

Particle size

As the particle size becomes smaller the surface area to volume ratio increases full stop the largest surface areas allow greater interactions with the solvent.


The temperature will affect solubility. An increase in temperature also increases solubility.


As the pressure increases, solubility also increases, and a decrease in pressure decreases solubility.

Nature of solute and solvent

This can be easily understood by one example. Only one gram of lead chloride can be dissolved in 100 grams of water at room temperature but at the same temperature, 200 grams of zinc chloride can be dissolved in the same amount of water. This is because of the differences in the nature of solute and solvent.


Generally, non-polar solute molecules will dissolve in the non-polar solvent and polar solid molecules will dissolve in polar solvents.


Polymorphs can have different melting points. Since the melting point of the solid is related to the solubility, so polymorphs will have different solubilities.

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