Factors Affecting Solubility of Drugs

Solubility is defined as the upper limit of solute that can be dissolved in a given amount of solvent at equilibrium. It is also called the ability of substance to dissolve in a solvent.
The solubility is defined as the concentration of the solute in solution when it is in equilibrium with the solid substance at a particular temperature.

A List of 10 Factors Affecting Solubility

  1. Temperature
  2. Molecular Structure
  3. Particle Size
  4. Nature of solvent and co-solvent
  5. Effect of complex formation
  6. Solubilizing agents
  7. Effect of pH
  8. Effect of additives
  9. Common ion effect
  10. Effect of Electrolytes and Non electrolytes

Temperature and Pressure

As per Henry’s Law, the solubility of a gas in a solvent depends on the pressure and the temperature. When a gas is enclosed over its saturated solution, the following equilibrium exists.
gas ⇌ gas in solution

If pressure is increased on the system, the equilibrium will move in the direction which will reduce the pressure (Le Chatelier Principle). The pressure can be reduced by more gas dissolving in solvent. Thus solubility or concentration of a gas in a given solvent is increased with increase of pressure.

Increase the temperature so, most solids increase the solubility of gas in liquid because the tendency of gas to expand in the temperature. For solids which dissolve with the evolution of heat, an increase in temperature causes decrease in the solubility. (Example: KNO3, NaCl).

Molecular Structure

Slight modification in the molecular structure of solids can result in the changes in solubility.

Nature of Solvent and Co-solvent

Addition of Solvent and Co-solvent increase the solubility of solids in liquids, those substances called as co-solvents. Example: Poorly soluble drugs are dissolved with addition of ethanol.

Effect of Complex Formation

When a complex is formed it results in increases or decreases of Solubility.

Solubilizing Agents

Addition of surfactant increases the solubility of solid in liquid and surface tension also decreases. Example: Addition of SLS a surfactant when added to a solid form in a liquid medium increases the solubility by increasing an intimate contact of solid with the liquid medium.

Effect of Additives

When large amount of additives are added then solubility increases and the process is called hydrotropy.

Particle Size

When particle size is small then the surface area large. So its results increase in the surface free energy, which increases the solubility of drug. Example: Hydrochlorothiazide (micronized)

Common Ion Effect

The reduction of the degree of dissociation of a salt by the addition of a common-ion is called the Common-ion effect. Let us consider a few examples to illustrate the common-ion effect.

Effect of Electrolytes and Non electrolytes

There is a decrease in the solubility of sparingly soluble salt in water when a non-electrolyte like alcohol is added, due to reduction in the dielectric constant. When an electrolyte is added the intermolecular force will decreases the solubility of non-electolyte.

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