Download Topic 8-Solubility-Modified

Solubility
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GENERAL PRINCIPLES
Definitions
Solubility


is defined in:
Qualitative terms: as the spontaneous
interaction of two or more substances to
form a homogeneous molecular dispersion.
Quantitative terms: as the concentration of
solute in a saturated solution at a certain
temperature.
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GENERAL PRINCIPLES
Definitions
Saturated
Solution
A solution in which the solute is in equilibrium with the
solid phase( the solute). It is when no more of the solid
will dissolve into the solution.
Unsaturated
Solution
A solution in which the concentration of the solute is
below that which is necessary for a saturated solution.
Supersaturated
Solution
A solution that contains more of the dissolved solute
than it would normally contain at a definite temperature.
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GENERAL PRINCIPLES
Solubility expressions:
The solubility of a drug may be expressed in a number of
ways.
 The USP and NF list the solubility of drugs as the
number of milliliters of solvent in which 1 gram of solute will
dissolve.
 Solubility is also quantitatively expressed in terms of
molality, molarity and percentage.
 Solubility can also be expressed by the use of certain
general terms, as given in the following table.

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Terms of solubility
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Solvent solute interaction
LIKE DISSOLVES LIKE. This means
that a polar solvent (high dielectric
constant) will dissolve a polar solute
and a nonpolar solvent (low dielectric
constant) will dissolve a nonpolar
solute.
 Classification of solvents:
A) Polar solvents.
B) Non polar solvents.
C) Semi-polar solvents.

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Solvent Polarity
Dielectric
constant, 
80
Solvent
Solute
water
Inorganic and organic salts
50
glycols
Sugars, tannins
30
methyl and ethyl alcohols
Caster oil, waxes
20
Aldehydes, ketones, and Resins, volatile oils, weak electrolytes
higher alcohols, ethers,
including barbiturates, alkaloids and
esters
phenols
Hexane, benzene, carbon Fixed oils, fats, petrolatum, paraffin,
tetrachloride, ethyl ether,
other hydrocarbons
petroleum ether
Mineral oil and fixed
vegetable oils
5
0
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Solvent solute interaction
A) Polar solvent: (e.g., water):

Polar solvents dissolve ionic solutes and other
polar substances .

Factors affecting water solubility:
a)


Polarity
Structural features such as:
the ratio of the polar to the non polar groups of the molecule.
Branching of the carbon chain decreases the nonpolar effect and
leads to increased water solubility.
b) The ability of the solute to form H-bonds
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Solvent solute interaction
A) Polar solvent: (e.g., water):
Polar solvents work by the following mechanisms:
(1) Owing to high dielectric constant; polar solvents reduce
ionic attraction between oppositely charged ions in
crystals.
(2) Break covalent bonds of strong electrolytes such as HCl
by acid-base reactions resulting in dissociation.
(3) Solvating molecules through dipole interaction forces
(particularly, hydrogen bond).
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Solvent - Solute Interactions
B) Nonpolar solvents (e.g. hydrocarbons):
dissolve nonpolar compounds through induced
dipole interactions. The solute molecules are kept
in solution by London forces.
C)
Semi
polar
alcohols):


solvents
(ketones,
Can induce polarity in non-polar solvent molecules.
They may act as intermediate solvents to bring about
miscibility between polar and non polar solvents.(cosolvents).
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The Solubility of Solids in Liquids
Ideal solution:
The solubility of a solid in an ideal solution is dependent
on temperature (T), melting point of the solid (Tₒ) , and
the molar heat of fusion (ΔHf).The molar heat of fusion is
the amount of heat absorbed when the solid melts. An
ideal solution is one which the heat of solution is equal to
the heat of fusion. The equation to explain the fact that
temperature, melting point, and molar heat of fusion
effect the solubility of a solid is:
 log x 2i 
 Hf  T0  T

2 .303 R  TT0



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The Solubility of Solids in Liquids
Non-ideal solution:

The activity of a solute (a2) in a solution is expressed as the concentration
(x2) multiplied by the activity coefficient (γ2), when the concentration is
given in mole fraction, the activity is expressed as:
a2 x2 2
log a2 log x2  log  2
The equation below explains the factors affecting the solubility in real solution.
Similar to that of ideal solutions: temperature, melting point, and molar heat
of fusion effect the solubility of a solid. In addition, the effect of solvent is to
be considered through the activity coefficient,
 log x 2 
 Hf  T0  T

2 .303 R  TT0

  log  2

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The Solubility of Solids in Liquids
Ideal vs. non-ideal solutions:
In summary, the previous relationships showed that ideal solubility is
NOT affected by the nature of the solvent, However, in real solutions,
the nature of the solvent (similarity or differences between solvent and
solute) is considered and expressed by the activity coefficient (γ2).
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Solubility of strong electrolytes

The temperature effects the solubility of
salts. The increase of temperature
increases the solubility of the solid that is
endothermic. That means that the solid
absorbs heat to dissolve in the solution.
The decrease of temperature causes the
increase in solubility in solids that are
exothermic. Exothermic means that the
solids release heat as they dissolve into
the solution.
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Solubility of strong electrolytes
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Solubility of weak electrolytes
The great majority of drugs are organic electrolytes and
therefore, four parameters determine their solubility:
Their degree of ionization, their molecular size, the
Interactions of substitute groups with solvent and their
crystal properties.
A} The influence of pH on aqueous solubility:
1} Acidic drugs: such as barbiturates, NSAID, nitrofurantoin,
phenyl butazone, are less soluble in acidic solutions than
in alkaline solutions because the predominant
undissociated species cannot interact with
water
molecules to the same extent as the ionized form which is
readily hydrated.

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Solubility of weak electrolytes
2} Basic drugs: Such as chlorpromazine are, more soluble in
acidic solution where the ionized form of the drug is
predominant.
3} Amphoteric drugs: have both basic and acidic characteristics
such as amino acids, sulphonamides, tetracyclines
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Solubility of weak electrolytes
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Solubility of weak electrolytes
B} The influence of solvents on the solubility of drugs:
Weak electrolytes may behave as strong electrolytes or as
non electrolytes ( depending on ionization).
For weak electrolytes and non electrolytes, there may be a
need to use mixed solvents when the solubility in one
solvent is limited or when the stability characteristics of
soluble salts forbid their use.
This phenomenon is called: cosolvency and solvents here
are called cosolvents.
Examples on water miscible solvents: Glycerol, Propylene
glycol, ethyl alcohol, polyoxyethylene glycols.
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Solubility of weak electrolytes
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