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SOLUBILITY OF DRUGS
Presented by:
Mahewash A. Pathan
SOLUBILITY
“ The concentration of a substance (solute) that
dissolves in a given volume of solvent at a certain
temperature to form a homogenous solution.”
OR
“ The spontaneous interaction of two or more
substances to form a homogenous molecular
dispersion.”
2
Definitions
• 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.
3
SOLUBILITY EXPRESSIONS
Sr.
No.
Description forms
( Solubility)
Parts of solvent required
for one part of solute
1 Very soluble (VS) <1
2 Poorly soluble (PS) 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
4
MECHANISM OF SOLUTE SOLVENT INTERACTIONS
“LIKE DISSOLVES LIKE”
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
5
IDEAL SOLUBILITY PARAMETERS
‘Ability of a liquid to act as a solvent’
1) Hildebrand solubility parameter (δ)
“ square root of cohesive energy density”
δ= √△Hv- RT/ Vm
2) Hansen solubility parameter (δt)
δt= δd + δp + δh
6
Solvation / Dissolution
“ Interaction of a solute with the solvent, which leads
to stabilization of solute species in the solution”
+ve solvation energy= endothermic dissolution
-ve solvation energy= exothermic dissolution
7
Association
“ Chemical reaction in which the opposite electric
charge ions come together in solution & form a
distinct chemical entity”
Classification according to nature of interaction:
1. Contact
2. Solvent shared
3. Solvent separated
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
SOLUBILITY OF GASES IN LIQUIDS
Henry’s law:
‘Solubility is directly proportional to partial pressure
of gas at a constant temperature’.
S= KP
10
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.
11
RAOULT’S LAW
“The partial pressure (Pi) of each component in a
solution is equal to the mole fraction of the
component & the vapour pressure of the pure
component”
Pi = xP
Or
P = pAxA + pBxB
12
IDEAL SOLUTIONS
“ Solutions which obey Raoult’s law in all the solute
composition in a solvent”
13
REAL/ NON IDEAL SOLUTIONS
“Solutions which do not obey Raoult’s law over entire
range of composition”
Negative deviation
PA < Xa P
△H < 0
△V < 0
Positive deviation
PA > Xa P
△H > 0
△V > 0 14
AZEOTROPES
(Constant boiling mixtures)
MINIMUM BOILING
AZEOTROPES
+ve deviation from Raoult’s law
MAXIMUM BOILING
AZEOTROPES
-ve deviation from Raoult’s law
15
FRACTIONAL DISTILLATION
16
CRITICAL SOLUTION TEMPERATURE
(CST)
17
NERNS’T DISTRIBUTION LAW
( PARTITION COEFFICIENT)
“ If a solute distributes
between two immiscible
solvents at a constant
temperature then the
ratio of its concentration
in two solvents is a
constant value”.
K= C1/ C2
18
THANK YOU…..
19

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Solubility of drugs

  • 1. SOLUBILITY OF DRUGS Presented by: Mahewash A. Pathan
  • 2. SOLUBILITY “ The concentration of a substance (solute) that dissolves in a given volume of solvent at a certain temperature to form a homogenous solution.” OR “ The spontaneous interaction of two or more substances to form a homogenous molecular dispersion.” 2
  • 3. Definitions • 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. 3
  • 4. SOLUBILITY EXPRESSIONS Sr. No. Description forms ( Solubility) Parts of solvent required for one part of solute 1 Very soluble (VS) <1 2 Poorly soluble (PS) 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 4
  • 5. MECHANISM OF SOLUTE SOLVENT INTERACTIONS “LIKE DISSOLVES LIKE” 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 5
  • 6. IDEAL SOLUBILITY PARAMETERS ‘Ability of a liquid to act as a solvent’ 1) Hildebrand solubility parameter (δ) “ square root of cohesive energy density” δ= √△Hv- RT/ Vm 2) Hansen solubility parameter (δt) δt= δd + δp + δh 6
  • 7. Solvation / Dissolution “ Interaction of a solute with the solvent, which leads to stabilization of solute species in the solution” +ve solvation energy= endothermic dissolution -ve solvation energy= exothermic dissolution 7
  • 8. Association “ Chemical reaction in which the opposite electric charge ions come together in solution & form a distinct chemical entity” Classification according to nature of interaction: 1. Contact 2. Solvent shared 3. Solvent separated 8
  • 9. 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
  • 10. SOLUBILITY OF GASES IN LIQUIDS Henry’s law: ‘Solubility is directly proportional to partial pressure of gas at a constant temperature’. S= KP 10
  • 11. 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. 11
  • 12. RAOULT’S LAW “The partial pressure (Pi) of each component in a solution is equal to the mole fraction of the component & the vapour pressure of the pure component” Pi = xP Or P = pAxA + pBxB 12
  • 13. IDEAL SOLUTIONS “ Solutions which obey Raoult’s law in all the solute composition in a solvent” 13
  • 14. REAL/ NON IDEAL SOLUTIONS “Solutions which do not obey Raoult’s law over entire range of composition” Negative deviation PA < Xa P △H < 0 △V < 0 Positive deviation PA > Xa P △H > 0 △V > 0 14
  • 15. AZEOTROPES (Constant boiling mixtures) MINIMUM BOILING AZEOTROPES +ve deviation from Raoult’s law MAXIMUM BOILING AZEOTROPES -ve deviation from Raoult’s law 15
  • 18. NERNS’T DISTRIBUTION LAW ( PARTITION COEFFICIENT) “ If a solute distributes between two immiscible solvents at a constant temperature then the ratio of its concentration in two solvents is a constant value”. K= C1/ C2 18