This document discusses the solubility of drugs. It defines solubility both quantitatively as the concentration of a substance that dissolves in a solvent to form a homogeneous solution, and qualitatively as the spontaneous interaction of substances to form a molecular dispersion. It describes key terms like solute, solvent, saturated and unsaturated solutions. It also discusses various quantitative and qualitative expressions used to describe solubility. Finally, it outlines several factors that can influence the solubility of a substance, such as temperature, nature of the solute and solvent, pressure, pH, particle size, molecular structure, and presence of solubilizing agents.

1. SOLUBILITY OF DRUGS
Presented by:
muhannad O. Taher

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SOLUBILITY
“ The concentration of a substance (solute) that
dissolves in a given volume of solvent at a certain
temperature to form a homogenous solution.”
quantitative terms
OR
“ The spontaneous interaction of two or more
substances to form a homogenous molecular
dispersion.” qualitative terms

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• Solute: a component which dissolved in the solvent, present in less
amount in the solution.
• Solvent: a component in which solute is dissolved, present in more
amount than solute.
• Solution: A system in which solutes are completely dissolved in
solvent & form a homogenous molecular dispersion.
• Saturated solution: Solution in which the solute in solution is in
equilibrium with solid phase.
• Unsaturated solution: Solution containing dissolved solute in
concentration below that necessary for complete saturation.
• Supersaturated solution: Solution containing more of the dissolved
solute than it would normally contain.

4. SOLUBILITY EXPRESSIONS
(quantitative)
• g/ml : Most commonly used method of expressing solubility. It
is the number of grams of solute that dissolves in one ml of the
solvent.
• Molarity : It is the number of moles (gram molecular weight) of
the solute in 1 litre of the solvent.
• Normality : It is the gram equivalent weight of the solute in
1litre of the solution.

5. SOLUBILITY EXPRESSIONS
• %w/w : It is the weight in grams of solute dissolved in 100 g of
solution.
• %w/v : It is the weight in grams of solute dissolved in 100 ml of
solution.
• %v/v : It is the volume of the solute in ml dissolved in 100 ml of the
solvent

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SOLUBILITY EXPRESSIONS
(qualitative)
Sr.
No.
Description forms
( Solubility)
Parts of solvent required
for one part of solute
1 Very soluble (VS) <1
2 Freely soluble (FS) 1-10
3 Soluble 10-30
4 Sparingly soluble (SPS) 30-100
5 Slightly soluble (SS) 100-1000
6 Very slightly soluble (VSS) 1000-10000
7 Practically insoluble (PI) >10000

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MECHANISM OF SOLUTE SOLVENT INTERACTIONS
Sr.
No
Nature of
Solvent
Mechanism of solubility Example
1. Polar a. High dielectric
constant
b. H- bond formation
c. dipole interactions
Water+ ethanol
2. Non-polar weak van der waal’s
forces
Fats, oils, alkaloidal
bases + CCL4,
benzene
3. Semi-polar induce certain degree of
polarity
Acetone increase
solubility of ether in
water

8. FACTORS INFLUENCING
SOLUBILITY
1. Temperature
2. Nature of solvent ( like dissolves like)
3. Pressure
4. pH
5. Particle size
6. Crystal structure
7. Molecular structure
8. Solute- solvent interactions
9. Addition of substituent
10. Common ion effect
11. Solubilizing agents 9

9. Temperature:
• If the process of dissolution is exothermic
then increase in temperature decreases the
solubility.
• If the process of dissolution is endothermic
then increase in temperature increases the
solubility.

10. Nature of the solute & solvent:
a. ‘like dissolves like’
A solute dissolves best in a solvent with similar
chemical properties. The concept traditionally
follows two rules:
1. Polar solutes dissolve in polar solvents.
2. Non-polar solutes dissolve in non-polar
solvents.

11. cosolvents
mixtures of solvents may be employed. This is achieved by
using cosolvents such as ethanol or propylene glycol, which
are miscible with water and which act as better solvents for
the solute in question.

12. Molecular structures
Presence of hydrophilic or hydrophobic groups within
the molecular structure greatly affects the solubility of
the compound.
• Introduction of a hydrophilic hydroxyl group can
produce a large improvement in water solubility
• Phenol is 100 times more soluble than benzene

13. Solubilizing agents
These agents are capable of forming large aggregates or
micelles in solution when their concentrations exceed
certain values.
Crystal structures & polymorphism
• Crystal structures : The amorphous forms of drugs are more
soluble than the crystalline forms.

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SOLUBILITY OF LIQUIDS IN LIQUIDS
1. Completely miscible liquids:
E.g. Water+ ethanol, Glycerine+ Alcohol, benzene+ CCL4
2. Partially miscible liquids:
E.g. Phenol+ water.
3. Completely immiscible liquids:
E.g. Mercury+ water.

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