Sunday, July 6, 2025 2:44 PM
• Solubility is defined in quantitative terms as the concentration of
solute in a saturated solution at a certain temperature, and in a
qualitative way, it can be defined as the spontaneous interaction of
two or more substances to form a homogeneous molecular dispersion.
• Solubility is an intrinsic material property that can be altered only by
chemical modification of the molecule
• In contrast to this, dissolution is an extrinsic material property that can
be influenced by various chemical, physical, or crystallographic means
such as complexation, particle size, surface properties, solid-state
modification, or solubilization enhancing formulation strategies.
• The equilibrium involves a balance of the energy of three interactions
against each other: (1) solvent with solvent, (2) solute with solute, and
(3) solvent and solute.
• Thermodynamic equilibrium is achieved when the overall lowest
energy state of the system is achieved.
Solubility Expressions
• The solubility of a drug may be expressed in a number of ways.
The United States Pharmacopeia (USP) describes the solubility of
drugs as parts of solvent required for one part solute.
• The USP describes solubility using the seven groups.
• The European Pharmacopoeia lists six categories.
• Solubility is also quantitatively expressed in terms of
molality, molarity, and percentage
•% w/w; no of grams of solute dissolved in 100 grams of solution
•% v/v; no of ml of solute dissolved in 100 ml of solution
•% w/v; no of grams of solute dissolved in 100 ml of solution
•Molarity; no of moles of solute dissolved in 1 liter of solution
•Molality; no of moles of solute dissolved in 1000 g of solvent
In pharmaceutical sciences, solubility is a key
parameter used to categorize drug substances.
Gases in Liquids
• The solubility of a gas in a liquid represents the concentration of
dissolved gas in the liquid when it is in equilibrium with some of the
pure gas above the solution.
• Pharmaceutical aerosols having nitrogen or carbon dioxide as a
propellant
• Effervescent preparations containing dissolved carbon dioxide
Solubility of gas in a liquid solvent depends on
1. Temperature dec and pressure (Significantly changes the solubility of dissolved gas)
2. Chemical Reaction if any between the gas and the solvent generally
solubility of gases.
3. Presence of Salts(Solubility of a gases in a solvent is generally
reduced by the addition of electrolytes such as sodium chloride or
non-electrolytes such as sugar) cz of salting out.More affinity b/w the solvent &
electrolyte or non-electrolyte than b/w the solvent and the gas.
Salting out is a purification technique used to separate molecules,
often proteins or DNA, from a solution by decreasing their solubility
through the addition of a high concentration of a salt. This causes
the target molecules to precipitate out of the solution, allowing for
their collection.
FACTORS AFFECTING SOLUBILITY OF LIQUIDS IN LIQUIDS
Examples of pharmaceutical solutions containing a liquid dissolved
in another liquid includes;
• Hydro-alcohlic solutions
• Aromatic waters such as peppermint water
• Elixirs
• Medicated oils (having two or more miscible oils.
Liquid–liquid systems can be divided into two categories according
to the solubility of the substances in one another:
(a) complete miscibility and
(b) partial miscibility
©Practically immiscible
The term miscibility refers to the mutual solubility's of the components
in liquid-liquid systems.
The temperature at which two partially miscible liquids becomes completely miscible resulting in a
homogenous or single phase in all proportions is called as critical solution temperature or
consulate temperature
With some liquid pairs such as triethylamine and water, the solubility can increase as the
temperature is lowered The system exhibit a lower consolute temperature Meaning that below
this temperature the two components are soluble in all proportions and above which two
separate layers form
For certain systems such as solution of phenol & water, the mutual solubility's of the two
conjugate liquid phases increases with temperature Such system show an upper critical solution
temperature (or upper consulate temperature)
Phenomenon of increasing the solubility of poorly soluble substances by the
use of more than one solvent is termed as co-solvency
Solubility of weak electrolytes and nonpolar molecules in water may be
enhanced by the addition of co-solvents; ethanol or propylene glycol
Act via decreasing the interfacial tension b/w the hydrophobic solute and
aqueous environment or by altering the dielectric constant of the medium
1. Aqueous solubility of metronidazole is about 100mg/10mL
2. Adding water-miscible cosolvents can significantly increase its solubility
(500mg/10 mL)
