Transcript 9.용해도 및 분배현상 - Physical Pharmacy Laboratory

SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
1.
2.
3.
Definitions
Solubility Expressions
Factors Affecting Solubility
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
USP Chart of Descriptive terms
Term
대한약전 제 11개정
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

  
 

 
  
   
  
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실


Temperature
S e
 H so ln
RT
Pressure
log
S(T2 )
S(T1 )
H soln T2  T1

(
)
2.303R T2T1
C2 = σp


pH
Chemical Structures
- Dipole moment
- Dielectric properties
- Hydrogen bonding
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
1.
2.
3.
Polar Solvents
Nonpolar Solvents
Semipolar Solvents
“Like Dissolves Like”
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
(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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
(dissolve nonpolar solutes)

Influential Factors
•
•
Induced dipole interactions
Weak van der Waals-London type forces

Hydrocarbons
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
(Intermediate solvents)

Influential Factors
•
Induce a certain degree of polarity in non-polar solvent
molecules

Ketones and alcohols
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
1.
2.
3.
4.
5.
Effect of Pressure
Effect of Temperature
Salting Out
Effect of Chemical Reaction
Solubility Calculations
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

As the temperature increases, the solubility of most gases
decreases, owing to the greater tendency of the gas to expand
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

Gases (HCl, NH3, CO2) + Solvent
→ Chemical reaction
→ Increase solubility
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

Inverse Henry’s law constant, 
C2 =  P

Bunsen absorption coefficient, 
Vgas. STP
Vsoln.
= P
 : 일정 온도, gas의 partial pressure 1 기압하에 solvent 1L
에 녹 는 gas의 volume (L)
Satuated condition : 0℃, 760mmHg
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
1.
2.
3.
4.
Ideal and Real Solutions
Complete Miscibility vs Partial Miscibility
Influence of Foreign Substances
Influence of Solvents on Solubility
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

Ideal Solutions

Pi  Pi  X i
Raoult’s Law:
0
Nonideal Solutions
a. Negative deviation
b. Positive deviation
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

Negative deviation
A
A
A
B
Associated with hydrogen bonding
between polar comp
Increased solubility
Chloroform & acetone
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

Positive deviation
A
A
A
B
Cannot mingle with each other
Partial solubility
Decreased solubility
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
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 nonpolar liquid is increased by a
micelle-forming surface-active
agent

SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
W22
(a)
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)
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

Solubility Parameter
H v  RT 12
 (
)
Vl
ΔHv = the heat of vaporization
Vl = the molar volume of the liquid at the desired temperature

lnr 2  w 11   w 22 
1/2
logr2  δ 1  δ 2 
2

1/2 2
v 2Φ12
RT
V2Φ12
2.303RT
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

Solvation
- 2w12 > w11 + w22
-H = negative
v
- negative
deviation from
Raoult’s law

Association
- interaction occurs between like
molecules of one of the
components in a solution
-H = positive
v
- positive
deviation from
Raoult’s law
V2Φ12
lnr 2  (w 22  w 11  2w 12 )
RT
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

∆Hsoln : heat of solution
H so ln T ' 'T '
ln( c' ' / c' ) 
(
)
vR
T 'T ' '
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

Weak Acids

HA  H   A
Ka 


[ H ][ A ]
[ HA]
Weak Bases
B  BH   OH 
[ BH  ]  [OH  ]
Kb 
[ B]
S0 K a
S  S0 
[ H 3O  ]
S  S0
pHp  pK a  log
S0
S0
pHp  pK a  log
S  S0
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
The solubility of
phenobarbital in a
mixture of water,
alcohol, and
glycerin at 25℃
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실
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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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 base,
For a weak organic

Kd 
C0
Cw
[ HA]0
Kd 
[ HA]w
[ B ]0
Kd 
[ B ]w
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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  K d [ 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  ]
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실

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
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실






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)
SKKU Physical Pharmacy Laboratory
성균관대학교 물리약학연구실