1. Solubility and Partition Phenomena

2. Contents General Principles Solvent-Solute Interactions
Solubility of Gases in Liquids
Solubility of Liquids in Liquids
Solubility of Solids in Liquids
Partition Phenomena

3. Ⅰ. General Principles Definitions Solubility Expressions
Factors Affecting Solubility

4. Definitions Solution : a liquid in which a solid substance has been
dissolved.
Solute : a solid substance that is dissolved in a liquid.
Solvent : a liquid that can dissolve other substances.
Solubility :
the concentration of solute in a saturated solution at equilibrium at a given temperature
given as per weight or volume of solvent
g (solute) / 100g (solvent)
1g (solute) / volume (ml) of solvent

5. Unsaturated or Subsaturated Solution
the solute is in equilibrium with the solid phase
Unsaturated or Subsaturated Solution
one containing the dissolved solute in a concentration that necessary for complete saturation at a definite temperature
Supersaturated Solution
one that contains more of the dissolved solute than it would normally contain at a definite temperature

6. Miscible
the solute when it is a liquid and will form a solution with a solvent over any concentration range
The Phase Rule
F = C – P + 2

7. Solubility Expressions
대한약전 제 8개정
USP Chart of Descriptive terms
Term
Parts solvent to 1 part solute
Very soluble
Less than 1
Freely soluble
1-10 (3-10%)
Soluble
10-30
Sparingly soluble
30-100
Slightly soluble
Very slightly soluble
,000
Practically insoluble, insoluble
More than 10,000 용어
썩 잘 녹는다
잘 녹는다
녹는다
조금 녹는다
녹이 어렵다
매우 녹기 어렵다
거의 녹지 않는다

8. Factors Affecting Solubility
Temperature
Pressure
C2 = σp pH
Chemical Structures
- Dipole moment
- Dielectric properties
- Hydrogen bonding

9. Ⅱ. Solvent – Solute Interactions
Polar Solvents
Nonpolar Solvents
Semipolar Solvents
“Like Dissolves Like”

10. Polar Solvents Influential Factors Mechanism Water Dipole moment
(dissolve ionic solutes and other polar substances)
Influential Factors
Dipole moment
Hydrogen bonds
Acidic and basic character of constituents
Structural features
Mechanism
High dielectric constant
Amphiprotic
Dipole interaction force
Water

11. Non-polar Solvents Influential Factors Hydrocarbons
(dissolve nonpolar solutes)
Influential Factors
Induced dipole interactions
Weak van der Waals-London type forces
Hydrocarbons

12. Semi-polar Solvents
(Intermediate solvents)
Influential Factors
Induce a certain degree of polarity in non-polar solvent molecules
Ketones and alcohols

13. Ⅲ. Solubility of Gases in Liquids
Effect of Pressure
Effect of Temperature
Salting Out
Effect of Chemical Reaction
Solubility Calculations

14. Effect of Pressure C2 = σp Henry’s Law
C2 = concentration of the dissolve gas (g/l)
p = partial pressure (mm of the undissolve gas)
σ = inverse of the Henry’s law constant, K
in a dilute solution at constant temperature, the concentration of dissolved gas is proportional to the partial pressure of the gas above the solution at equilibrium

15. Effect of Temperature
As the temperature increases, the solubility of most gases decreases, owing to the greater tendency of the gas to expand

16. Salting Out
Gases are often liberated from solutions in which they are dissolved by the introduction of an electrolytes and sometimes by a nonelectrolyte
NaCl
gases
sucrose
carbonated
solution

17. Effect of Chemical Reaction
Gases (HCl, NH3, CO2) + Solvent
→ Chemical reaction
→ Increase solubility

18. Solubility Calculations
Inverse Henry’s law constant, 
C2 =  P
Bunsen absorption coefficient, 
 : 일정 온도, gas의 partial pressure 1 기압하에 solvent 1L
에 녹 는 gas의 volume (L)
Satuated condition : 0℃, 760mmHg
Vgas. STP
Vsoln.
=  P

19. Ⅳ Solubility of Liquids in Liquids
Ideal and Real Solutions
Complete Miscibility vs Partial Miscibility
Influence of Foreign Substances
Influence of Solvents on Solubility

20. Ideal and Real Solutions
Ideal Solutions
Raoult’s Law:
Nonideal Solutions
a. Negative deviation
b. Positive deviation

21. Raoult’s Law Negative deviation A B
Associated with hydrogen bonding between polar comp A B
Increased solubility
Chloroform & acetone

22. Raoult’s Law Positive deviation A A B A Cannot mingle with each other
Partial solubility
Decreased solubility

23. Miscibility Complete Miscibility Partial Miscibility
Solvents are said to be completely miscible when they are mix in all proportions
Partial Miscibility
When certain amounts of two liquids are mixed, two liquid layers are formed, each containing some of the other liquid in the dissolved state

24. Miscibility

25. Influence of Foreign Substances
Binary addition Ternary
If the added material is soluble in only one of the two components / if the solubilities in the two liquids are markedly different
mutual solubility of the liquid pair is decreased
When the third substance is soluble in both of the liquids roughly the same extent
the mutual solubility of the
liquid pair is increased
Blending : the increase in mutual solubility of two partially miscible solvents by another agent
Micellar Solubilization : solubility in water of a non-polar liquid is increased by a micelle-forming surface-active agent

26. Ⅴ Solubility of Solids in Liquids
Ideal Solutions
Nonideal Solutions
Solvation and Association in Solutions of Polar Compounds
Solubility and the Heat of Solution
Solubility of Strong Electrolytes
Solubility of Slightly Soluble Electrolytes
Solubility of Weak Acids and Weak Bases in Water as Influenced by pH
The Influence of Solvents on the Solubility of Drugs

27. Ideal Solutions
Depends on temperature, melting point of the solid, and molar heat of fusion
T = absolute temp. of the solution
T0 = melting point of the solid solute
X2i = ideal solubility of the solute expressed in mole fraction
∆Hf = Heat of solutions → Heat of fusion
Heat of solution = Heat of fusion
Not affected by the nature of the solvent
No longer applies when T > T0 and at temperatures
considerably below the melting point

28. Nonideal Solutions T = absolute temp. of the solution
T0 = melting point of the solid solute
∆Hf = Heat of solutions → Heat of fusion
γ2 = the mole fraction scale is known as the rational activity
coefficient
log γ2 : intermolecular forces of attraction in removing a molecule
from the solute phase and depositing it in the solvent

29. Liberation of a molecule from
W22
solute
Liberation of a molecule from
the solute
(b)
W11
solvent
Creation of a hole in the solvent
(c)
-2W12
solute
molecule
solution
solvent
Total work : (W22 + W11 -2W12)

30. Solubility Parameter ΔHv = the heat of vaporization
Vl = the molar volume of the liquid at the desired temperature

31. Solvation and Association in Solutions of Polar Compounds
- 2w12 > w11 + w22
= negative
- negative deviation from Raoult’s law
Association
- interaction occurs between like molecules of one of the components in a solution
= positive
- positive deviation from Raoult’s law

32. Solubility and the Heat of Solution
∆Hsoln : heat of solution

33. Solubility of Strong Electrolytes
Exothermic process
(heat is evolved)
the solubility decreases with an elevation of the temperature
Endothermic process
(absorbs heat)
a rise in temperature increases the solubility of a solid

34. Solubility of Slightly Soluble Electrolytes
Solubility product, :
the real solution solubility of poorly soluble strong electrolytes in water is calculated by using the solubility product constant obtained from thermodynamics
Common ion :
adding a common ion is to reduce the solubility of a slightly soluble electrolyte

35. Solubility of Weak Acids and Weak Bases in Water as Influenced by pH

36. The Influence of Solvents on the Solubility of Drugs
Strong Electrolytes :
strong acids and bases and all salts are soluble in water
Weak Electrolytes :
weak acids and bases with high molecular weight are not soluble in water
Nonelectrolytes :
high-molecular-weight organic drugs that do not dissociate or associate in water are generally soluble in organic solvents and have little or no solubility in water
Cosolvency :
a solute is more soluble in a mixture of solvents than in one solvent alone

37. Cosolvency
The solubility of phenobarbital in a mixture of water, alcohol, and glycerin at 25℃

38. Ⅵ. Partition Phenomena General Partitioning Concepts
For Strong Electrolytes as Solutes
For Nonelectrolyte Solutes
For Weak Electrolytes as Solutes
Application of Distribution Concepts
Drug Action / Absorption
Site of Drug Partitioning Considering pH Effects Alone

39. General Paritioning Concepts
The partition law :
a solute will distribute itself between two immiscible solvents so that the ratio of its conc. in each solvent is equal to the ratio of its solubility in each one
Co = molar conc. in organic layer
Cw = molar conc. in aqueous layer
Kd = partition coefficient or distribution constant

40. For Strong / Nonelectrolytes as Solutes
Strong Electrolyte
Strong electrolytes are completely dissociated in aqueous solution
→ cations & anions in aqueous layer
→ water soluble
Without ion pairing, do not partition into the organic layer
Nonelectrolyte

41. For Weak Electrolytes as Solutes
The partition law : depends on pH
pH different from pKa
(pH < pKa for weak acid ; pH > pKa for weak base)
For a weak organic acid,
For a weak organic base,

42. Application of Distribution Concepts
Preservation of Emulsions
The total preservative added = C, where C = C0 + Cw

43. Drug Action / Absorption
; by passive diffusion
; due only to a concentration gradient across the barrier
Drug Absorption
; water solubility of the drug, the lipid/water partition coefficient of the drug molecule, MW, chemical structure
; drugs must be in solution in aqueous intestinal fluids

44. Site of Drug Partitioning Considering pH Effects Alone
Absorption from the stomach (pH 1-3)
Absorption from the intestines (pH 4-6)
Urinary Excretion (pH 5-7)
Excretion of drugs in sweat (pH 5-7)
Excretion of drugs in human milk (pH 6.6)
Rectal administration (pH 7.8)