By: Denlo Jay Asuncion

School of Pharmacy
Centro Escolar University
 Solution
• A homogenous system in
which the solute is molecularly
dispersed, or dissolved in a
solvent
 Components of a Solution
• Solvent
–Present in greatest quantity
•Polar
•Nonpolar
•Semipolar
 Components of a Solution
• Solute
–Can be a gas, liquid, or solid
–MAIN CLASSES
•Nonelectrolytes
•Electrolytes
 The Solute: Nonelectrolytes
• Do not form ions when dissolved in water
• Do not conduct electric current
• Examples:
– Estradiol
– Glycerin
– Urea
– Sucrose
 The Solute: Electrolytes
• Form ions in solution and conduct electricity
• CLASSIFIED AS:
– Strong electrolytes
• Completely ionized in water
• Example: Sodium chloride and HCl
– Weak electrolytes
• Partially ionized in water
• Example: Aspirin and atropine
 The Solvent: Polar Solvents
• Dissolve ionic solutes and other polar
substance
• The solubility of various solutes in water may
be due to;
– Dipole moment
– Hydrogen bonds (dissolves phenols,
alcohols, aldehydes, ketones, amines and
other O and N containing compounds
 The Solvent: Polar Solvents
• The solubility of various solutes in water
may be due to;
– Difference in acidic and basic character of
the constituents
– Structural features such as the ratio of the
polar to the nonpolar groups of the
molecule
Solubility of substances is affected by
structural features

As the number of
nonpolar chain of an
aliphatic alcohol
increases, solubility in
water decreases
Solubility of substances is affected by
structural features
Straight-chain monohydroxy
alcohols, aldehydes, ketones, and
acids with more than 4 or 5 C
cannot enter into the hydrogen
bonded structure of water and
hence are only slightly soluble.
Solubility of substances is affected by
structural features
Water solubility increases when
additional polar groups are
present in the molecule as
found in propylene glycol,
glycerin and tartaric acid.
Solubility of substances is affected by
structural features

Branching of C-chain reduces

the nonpolar effect and leads
to increase water solubility.
 Mechanism of Solvent Action: For
Polar Solvents
1. High dielectric constant
2. Break covalent bonds of potentially strong
electrolytes by acid-base reactions
– HCl + H2O→H3O+ + Cl-
3. Capable of solvating molecules and ions
through dipole interaction force, particularly
H-bond formation.
 THE SOLVENT: NONPOLAR

Hydrocarbons.
Unable to reduce attraction
between ions of strong and weak
electrolytes due to low dielectric
constant.
 THE SOLVENT: NONPOLAR

Aprotic solvents (neither accept

nor donate protons), so cannot
break covalent bonds and
ionize weak electrolytes
 THE SOLVENT: NONPOLAR

Can dissolve nonpolar solutes with

similar internal pressures through
induced-dipole interactions
 THE SOLVENT: NONPOLAR

Ionic and polar solutes are not

soluble or are only slightly soluble
 THE SOLVENT: NONPOLAR
Examples:
• CCl4, benzene and mineral oil
– dissolve oils and fats
• Alkaloidal bases and fatty acids
– soluble in nonpolar solvents
 The Solvent: Semipolar

May act as intermediate

solvents to bring out the
miscibility of polar and
nonpolar liquids
 The Solvent: Semipolar
• Examples;
– Acetone – increases the solubility of ether
in water
– Alcohol – increases miscibility of water-
castor oil mixture
– Propylene glycol – increases miscibility of
water and peppermint oil; water and benzyl
benzoate
Quantitative Definition: Solubility

The concentration of solute

in a saturated solution at
certain temperature
Qualitative Definition: Solubility

The spontaneous interaction of

two or more substances to form
homogenous molecular
dispersion
 Descriptive Terms of Approximate
Solubility
Descriptive Term Parts of solvent required to dissolve 1
part of solute
VERY SOLUBLE Less than 1 part

FREELY SOLUBLE 1 – 10 parts

SOLUBLE 10 – 30 parts

SPARINGLY SOLUBLE 30 – 100 parts

SLIGHTLY SOLUBLE 100 – 1,000 parts

VERY SLIGHTLY SOLUBLE 1,000 – 10,000 parts

PRACTICALLY INSOLUBLE OR More than 10,000 parts

INSOLUBLE
 Solutions and Solubilty
• Saturated solution
– is one in which the solute is in equilibrium with the
solid phase (solute)
• Unsaturated or subsaturated solution
– Is one containing the dissolve solute in a
concentration below that necessary for complete
saturation at a definite temperature.
• Supersaturated solution
– Is one that contains more of the dissolved solute that
it would normally contain at a definite temperature,
were the undissolved solute is present
Factors affecting Solubility of Gases

1. Pressure
2. Temperature
3. Salting-out
4. Chemical reactions
 Effect of Pressure
• Expressed by Henry’s Law
• The weight of gas dissolved by a
given amount of a liquid at a given
temperature is proportional to its
pressure
 Effect of Temperature
• As the temperature increases, the
solubility of a gas in liquids decreases
• More gas is present in a solution with a
lower temperature compared to a
solution with a higher temperature.
 Salting-out
• A phenomenon where gases are often
liberated from solutions in which they
are dissolved by the introduction of an
electrolyte (NaCl) and sometimes by a
non-electrolyte (sucrose)
• May also occur in solutions of liquid-
liquid or solid-liquid
 Effect of Chemical Reaction
• Gases that can chemically react with
solvents such as HCl, ammonia, and CO2
are more soluble than those that do not
react with the solvent.
• HCl is about 10,000 times more soluble in
water than oxygen
Liquid-liquid Pharmaceutical Solutions

• Spirits
• Collodions
• Elixir
• Aromatic waters
Categories of Liquid-Liquid System
• Complete miscibility
– Liquids that mix in all proportions
– Examples: Water-alcohol; glycerin-alcohol;
alcohol-acetone; benzene-CCl4
• Partial miscibility
– When liquids are mixed, two layers are formed,
each containing some of the
– other liquid in dissolved state
– Examples: water-ether; water-phenol
 Factors Affecting the Miscibility of
Liquids in Liquids
• Influence of a foreign substance
• Dielectric constant
• Molecular connectivity
• Molecular surface area
 Influence of a Foreign Substance
• If the added material is soluble in only one of
the two components or if the solubilities in
the two liquids are markedly different, the
mutual solubility of the liquid pair is
decreased.
 Influence of a Foreign Substance
• When the third substance is soluble in both of
the liquids to roughly the same extent, the
mutual solubility of the liquid pair is
increased.
– Example: Glycerin in phenol-water system
• BLENDING
– Is the increase in mutual solubility of two partially
miscible solvents by another agent
 Ideal Solution
• Is one in which there is no change in the
properties of the components, other than
dilution, when they are mixed to form the
solution
• No heat is evolved or absorbed during the
mixing process
 Ideal Solution
• The solubility of solids depends on;
– Temperature
– Melting point
– Molar Heat of Fusion – the heat absorbed when
the solid melts
• The Heat of solution is equal to the heat of
fusion.
 Non-ideal Solution
• The heat of solution has a positive (energy
absorbed) or negative (energy liberated) value
• A negative heat of solution favors solubility
while a positive heat works against dissolution
 Solubility of Strong Electrolytes
The process of dissolution is generally
accompanied by;
1. ABSORPTION OF HEAT (Endothermic)
– The solution becomes cold
– Increase in temperature, increases solubility
– Dissolution of Na2SO4.H2O
 Solubility of Strong Electrolytes
2. EVOLUTION OF HEAT
– Exothermic (the solution is hot)
– Solubility decreases with an elevation of the
temperature
– Dissolution of anhydrous Na2SO4
– Sodium chloride does not evolve or absorb heat
when it dissolves in water, thus its solubility is not
altered much by a change of temperature, and
the heat of solution is zero.
Effect of Temperature on Solubility
• Decrease in solubility with temperature
(exothermic)
• Increase in solubility with temperature
(endothermic)
 Common-ion Effect
• Reduces the solubility of a slightly soluble
electrolytes
• When the common ion forms a complex with
the salt, the net solubility may be increased
 Common-ion Effect
• Example: If an ion common with AgCl
(e.g. Ag+ or Cl-) is added, the equilibrium
is altered
• AgCl + NaCl  AgCl()
• Some of the AgCl precipitates due to the
increase in Cl ion concentration
 Solubility of Weak Electrolytes
• CARBOXYLIC ACIDS WITH MORE THAN 5
CARBONS
– Insoluble in water
– Forms soluble salts with the addition of NaOH
• FATTY ACIDS WITH MORE THAN 10 CARBONS
(Oleic acid, C17H33COOH)
– Soluble in solvents with low dielectric constant
(alcohol and ether)
– Form soluble soap with alkali metal and insoluble
soap with other metal
 Solubility of Weak Electrolytes
• HYDROXY ACIDS (Tartaric acid and citric acid)
– Soluble in water through their OH-
• AROMATIC ACIDS
– Form precipitate with acids
– Form water-soluble salts with dilute alkalies
 Solubility of Weak Electrolytes
• ALKALOIDS, SYMPATHOMIMETIC AMINES,
ANTIHISTAMINES, LOCAL ANESTHETICS
– Soluble in dilute acid solution
• SULFONAMIDES
– Form slightly soluble weak acids and water-
soluble salts in alkaline solution
• BARBITURATES
– Soluble in alkalies
– Precipitated as free acid in strong acid
 Solubility of Weak electrolytes as
Influenced by pH
• Salt of weak acids precipitate in lower pH
– Na phenobarbital precipitates at pH below
8.3
• Salt of weak base precipitate when the
pH is elevated
– Codeine sulfate precipitates at an alkaline
pH
Influence of Solvents on the Solubility
of Weak electrolytes
• Weak acids and weak bases with high
MW are not soluble in water
• Co-solvents such as alcohol, propylene
glycol, and polyethylene glycol or mixed
solvent systems are required for their
solubility
 Solvent Effects on theSolubility of
Weak Electrolytes in Buffer Solution
1. Addition of alcohol increases the solubility of
the unionized species by adjusting the
polarity of the solvent to a more favorable
value
2. Alcohol decreases dissociation of weak
electrolytes, and solubility of the drug goes
down as the dissociation constant is
decreased
 Influence of other factors on the
solubility of solid
• Particle size
– Solubility increases with a decrease in particle size
• Configuration of molecule and the kind of
arrangement in the crystal
– -alanine – solubility is 1.66 moles/L
– -amino-n-butyric acid – solubility is 1.8 moles/L
– Less compact crystal has high solubility