Transcript Chapter 6 Solubility and Partition Phenomena

Solubility and Partition
Phenomena
Contents
I.
II.
III.
IV.
V.
VI.
General Principles
Solvent-Solute Interactions
Solubility of Gases in Liquids
Solubility of Liquids in Liquids
Solubility of Solids in Liquids
Partition Phenomena
Ⅰ. General Principles
1. Definitions
2. Solubility Expressions
3. Factors Affecting Solubility
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
 Saturated 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
 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
Solubility Expressions
USP Chart of Descriptive terms
Term
대한약전 제 8개정
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
100-1000
Very slightly soluble
1000-10,000
Practically insoluble,
insoluble
More than 10,000

  
 

 
  
   
  
Factors Affecting Solubility
 Temperature
S e
 H so ln
RT
 Pressure
C2 = σp
 pH
 Chemical Structures
- Dipole moment
- Dielectric properties
- Hydrogen bonding
log
S (T2 )
S (T1 )
H so ln T2  T1

(
)
2.303 R T2T1
Ⅱ. Solvent – Solute Interactions
1.
2.
3.
Polar Solvents
Nonpolar Solvents
Semipolar Solvents
“Like Dissolves Like”
Polar Solvents
(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
Non-polar Solvents (dissolve nonpolar solutes)
 Influential Factors
• Induced dipole interactions
• Weak van der Waals-London type forces
 Hydrocarbons
Semi-polar Solvents(Intermediate solvents)
 Influential Factors
•
Induce a certain degree of polarity in non-polar solvent molecules
 Ketones and alcohols
Ⅲ. Solubility of Gases in Liquids
1.
2.
3.
4.
5.
Effect of Pressure
Effect of Temperature
Salting Out
Effect of Chemical Reaction
Solubility Calculations
Effect of Pressure
 Henry’s Law
C2 = σp
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
Effect of Temperature
 As the temperature increases, the solubility of most gases
decreases, owing to the greater tendency of the gas to expand
Salting Out
 Gases are often liberated from solutions in which they are
dissolved by the introduction of an electrolytes and sometimes by a
nonelectrolyte
gases
NaCl
sucrose
carbonated
solution
Effect of Chemical Reaction
 Gases (HCl, NH3, CO2) + Solvent
→ Chemical reaction
→ Increase solubility
Solubility Calculations
 Inverse Henry’s law constant, 
C2 =  P
 Bunsen absorption coefficient, 
Vgas. STP
= P
Vsoln.
 : 일정 온도, gas의 partial pressure 1 기압하에 solvent 1L
에 녹 는 gas의 volume (L)
Satuated condition : 0℃, 760mmHg
Ⅳ Solubility of Liquids in Liquids
1.
2.
3.
4.
Ideal and Real Solutions
Complete Miscibility vs Partial Miscibility
Influence of Foreign Substances
Influence of Solvents on Solubility
Ideal and Real Solutions
 Ideal Solutions
Raoult’s Law:
 Nonideal Solutions
Pi  Pi  X i
0
a. Negative deviation
b. Positive deviation
Raoult’s Law
 Negative deviation
A
A
A
B
Associated with hydrogen bonding
between polar comp
Increased solubility
Chloroform & acetone
Raoult’s Law
 Positive deviation
A
A
A
B
Cannot mingle with each other
Partial solubility
Decreased solubility
Miscibility
 Complete 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
Miscibility
Influence of Foreign Substances
Binary
addition
 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
Ternary
 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
Ⅴ Solubility of Solids in Liquids
1.
2.
3.
4.
5.
6.
7.
8.
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
Ideal Solutions
Depends on temperature, melting point of the solid, and molar
heat of fusion
H f
T0  T
 log X 2 
(
)
2.303R T0T
i
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
Nonideal Solutions
H f
T0  T
 log X 2 
(
)  log 2
2.303RT T0
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
(a)
W22
Liberation of a molecule from
the solute
solute
(b)
W11
solvent
Creation of a hole in the solvent
(c)
-2W12
solute
solvent molecule
solution
Total work : (W22 + W11 -2W12)
 Solubility Parameter
H v  RT 12
 (
)
Vl
ΔHv = the heat of vaporization
Vl = the molar volume of the liquid at the desired temperature

lnr2  w 11   w 22 
1/2
logr2  δ 1  δ 2 
2
V2Φ12
2.303RT

1/2 2
v 2Φ12
RT
Solvation and Association in Solutions of Polar
Compounds
 Solvation
- 2w12 > w11 + w22
- H v = negative
- negative deviation from Raoult’s
law
V2Φ12
lnr2  (w22  w 11  2w12 )
RT
 Association
- interaction occurs between like
molecules of one of the
components in a solution
- H v = positive
- positive deviation from Raoult’s
law
Solubility and the Heat of Solution
 ∆Hsoln : heat of solution
H so ln T ' 'T '
ln(c' ' / c' ) 
(
)
vR
T 'T ' '
Solubility of Strong Electrolytes
 Endothermic process
(absorbs heat)
a rise in temperature increases the
solubility of a solid
 Exothermic process
(heat is evolved)
the solubility decreases with an
elevation of the temperature
Solubility of Slightly Soluble Electrolytes
 Solubility product,
: K sp
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
Solubility of Weak Acids and Weak Bases in
Water as Influenced by pH
 Weak Acids
 Weak Bases
HA  H   A
Ka 


[ H ][ A ]
[ HA]
B  BH   OH 
[ BH  ]  [OH  ]
Kb 
[ B]
S0 K a
S  S0 
[ H 3O  ]
S  S0
pHp  pKa  log
S0
S0
pHp  pKa  log
S  S0
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
Cosolvency
The solubility of
phenobarbital in a
mixture of water,
alcohol, and
glycerin at 25℃
Ⅵ. Partition Phenomena
1.
2.
3.
4.
5.
6.
7.
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
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
C0
Kd 
Cw
Co = molar conc. in organic layer
Cw = molar conc. in aqueous layer
Kd = partition coefficient or distribution constant
For Strong / Nonelectrolytes as Solutes
Strong Electrolyte
Nonelectrolyte
 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
Kd  O
Kd
C0

Cw
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,
C0
Kd 
Cw
[ HA]0
Kd 
[ HA]w
 For a weak organic base,
C0
Kd 
Cw
[ B ]0
Kd 
[ B ]w
Application of Distribution Concepts
 Preservation of Emulsions
The total preservative added = C, where C = C0 + Cw
C  [ HA]0  [ HA]w  [ A ]w
[ HA]0
Kd 
[ HA]w
[ HA]0  Kd [ HA]w
[ H 3O  ][ A ]w
K [ HA]w
Ka 
 [ A ]w  a
[ HA]w
[ H 3O  ]
C  K d [ HA]w  [ HA]w  K a
Ka
 [ HA]w ( K d  1 
)

[ H 3O ]
[ HA]w
[ H 3O  ]
[ HA]w 
C
Ka
Kd 1
[ H 3O  ]
Drug Action / Absorption
 Drug Action
; 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
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)