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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
Hydrocarbons.
Unable to reduce attraction
between ions of strong and weak
electrolytes due to low dielectric
constant.
THE SOLVENT: NONPOLAR
SOLUBLE 10 – 30 parts
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