Physical Pharmacy: CHAPTER 5 Prediction of solubility

General principle: “Like dissolves like”

SOLUTION– a homogeneous dispersion of two or more Solute dissolves best in a solvent with similar chemical
substances in each other properties.
SOLUTE – the dissolved substance 1. Polar solutes dissolve in polar solvents.
SOLVENT – the dissolving medium 2. Non-polar solutes dissolve in nonpolar solvents.

3 MOST IMPORTANT TYPES OF SOLUTIONS METHODS OF EXPRESSING CONCENTRATION

• Solid in liquid 1. % (W/V, W/W, V/V)
• Liquid in liquid 2. Molarity (M)
• Gas in liquid 3. Molality (m)
4. Normality (N)
Dissolution - the transfer of molecules or ions from a solid state 5. Osmolarity or Osmolality
into solution 6. mole %
- rate of solution
PERCENTAGE SOLUTION
Solubility- the amount of solid that passes into solution when
equilibrium is established between the solution and excess wt. of solute (g)
% 𝒘/𝒗 = × 100
(undissolved) substance. vol. of solution (mL)
The solution that is obtained under these conditions is said to
be saturated. wt. of solute (g)
% 𝒘/𝒘 = × 100
Solubility of the solute in the solvent- referred to as the extent wt. of solution (g)
to which the dissolution proceeds under a given set of
experimental conditions vol. of solute (mL)
% 𝒗/𝒗 = × 100
vol. of solution (mL)
Miscibility- when the 2 components forming the solution are
either both gases or both liquids Molarity
no. of moles (n) wt. of solute (g)
𝑀= =
Solubility and Dissolution L solution MW x L solution
- are not the same and not necessarily related
Molality
- in practice high drug solubility is usually associated
no. of moles (n) wt. of solute (g)
with a high dissolution rate 𝑚= =
kg solvent MW x kg solvent
U.S.P. Descriptive Terms of Solubility
Normality
Description Parts of solvent that gram − equivalent wt. of solute (Equivalence)
𝑵=
dissolves 1 part of solute L solution
(mL)
GEW wt. (g)
N= g − Eq wt. =
L solution Equal wt.
Very soluble <1
molecular weight
Eq. wt =
Freely soluble 1 - 10 h

Final Equations:
Soluble 10 - 30 GEW wt. of solute (g)
N= 𝑵=
L solution eq. wt. of solute x L solution
Sparingly soluble 30 - 100
wt. of solute (g)
𝑵=
MW
Slightly soluble 100 - 1000 x L sol′n
h

Very slightly soluble 1,000-10,000 Where:

h= total + or – charge for salt
= # of replaceable H+ for acid
Practically soluble >10,000 = # of replaceable OH+ for base

2E-PH: Belmonte, Manalo, Sarto, Yan

 gram − equivalent wt. 1000mEq − wt.of solute Examples:
N= 1000mL x
L solution x 1Eq.wt.
1L 1. A solution is prepared by dissolving 64.92g of Magnesium
chloride in sufficient water to make 600 mL of solution. The
GmEq solute or milli − equivalence
N= density of the solution is 1.082 g/mL. (At. wt.: Mg = 24.31, Cl =
mL solution
35.45)
mEW =
1
x EW Calculate:
1000
a. Molality
1 MW b. mf of solute
mEW = x c. mole % solvent
1000 h
d. % by wt.
GmEW solute
N= e. Osmolarity
mL solution

wt.of solute (g) a. Molality

N=
mEW solute x mL solution G solution = 600 mL x 1.082g/mL
= 649.2g - 64.92g = 584.28g
wt.of solute (g)
N= MW 584.28g / 1000 = 0.58428kg
x mL solution
h x 1000
Mg (24.31) + Cl2(35.45 x 2) = 95.21MW
1𝑚𝑜𝑙
wt.of solute (g) wt.of solute (g) 64.92g x = 0.681861149mol
N= =mol.wt. 95.21𝑔
EW solute x L solution x L solution 𝑛 𝑜𝑓 𝑚𝑜𝑙𝑒𝑠 (𝑛) 0.681861149𝑚𝑜𝑙
h
m= = = 1.1670m
𝑘𝑔 𝑠𝑜𝑙𝑣𝑒𝑛𝑡 0.58428𝑘𝑔
wt.of solute (g) wt.of solute (g)
N= = MW
mEW solute x mL solution x mL solution b. Mf of solute
h x 1000
1 𝑚𝑜𝑙
N solute = 64.92g x = 0.6819mol MgCl2
95.21𝑔
N=Mxh 1 𝑚𝑜𝑙 𝐻2𝑂
N solvent = 584.28g H2O x = 32.46mol
18𝑔
𝑛 𝑠𝑜𝑙𝑢𝑡𝑒
Osmolarity = mOsmol /L solution Mf solute =
𝑛 𝑠𝑜𝑙𝑢𝑡𝑒 + 𝑛 𝑠𝑜𝑙𝑣𝑒𝑛𝑡
= (mmol x i) / L solution =
0.6819𝑚𝑜𝑙
= 0.02057mol
0.6819𝑚𝑜𝑙 + 32.46𝑚𝑜𝑙
= (moles x 1000 x i) / L solution
𝑊𝑡.
=( ) / L solution c. Mole % solvent
𝑚𝑜𝑙.𝑤𝑡.
= M x 1000 x i Mf solvent =
𝑛 𝑠𝑜𝑙𝑣𝑒𝑛𝑡
𝑛 𝑠𝑜𝑙𝑢𝑡𝑒 + 𝑛 𝑠𝑜𝑙𝑣𝑒𝑛𝑡
32.46𝑚𝑜𝑙
Osmolality = mOsmol /kg solvent = = 0.9794mol
0.6819𝑚𝑜𝑙 + 32.46𝑚𝑜𝑙
= (mmol x i) / kg solvent Mole % solvent = mf x 100
= (moles x 1000 x i) / kg solvent = 0.9794mol x 100 = 97.94%
𝑊𝑡.
=( ) / kg solvent
𝑚𝑜𝑙.𝑤𝑡.
d. % by weight
= m x 1000 x i 𝑤𝑡.𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒
= x 100
𝑤𝑡.𝑜𝑓 𝑠𝑜𝑙𝑛
64.92𝑔
Mole % = mole fraction (mf or X) x 100 = x 100 = 10%w/w
649.2𝑔

Mole % solute = mf solute (𝑋2 ) x 100

2. A solution of acetic acid is prepared by adding 164.2 g of the acid
to sufficient water to make 800 mL of solution at 20°C. The
Mole % solvent = mf solvent (𝑋1 ) x 100
density of the solution at this temperature is 1.026 g/mL. (At.
Where:
𝑛 𝑠𝑜𝑙𝑢𝑡𝑒
wt.: C = 12, H = 1, O = 16)
mf solute = Calculate:
𝑛 𝑠𝑜𝑙𝑢𝑡𝑒 + 𝑛 𝑠𝑜𝑙𝑣𝑒𝑛𝑡
𝑛 𝑠𝑜𝑙𝑣𝑒𝑛𝑡
mf solvent = a. Molarity
𝑛 𝑠𝑜𝑙𝑢𝑡𝑒 + 𝑛 𝑠𝑜𝑙𝑣𝑒𝑛𝑡
b. mf of solvent
mf solute + mf solvent = 1 c. mole % solute
d. % w/v
mole% solute + mole% solvent = 100% e. Osmolality
f. normality

2E-PH: Belmonte, Manalo, Sarto, Yan

SOLUTIONS OF GASES IN LIQUIDS Since : 𝑋1 = 1 − 𝑋2
1. Effect of pressure on the solubility 𝑃1 = 𝑃1 ° (1 − 𝑋2 )
● Solubility of a gas over a given solvent increases with
an increase in the partial pressure of the gas over the
If: 𝑃1 = 𝑃1 ° (1 − 𝑋2 )
solution
● Henry’s Law 𝑃1 = 𝑃1 ° − 𝑃1 ° 𝑋2
- the concentration of dissolved gas in a given solvent 𝑃1 ° − 𝑃1 = 𝑃1 ° 𝑋2
is directly proportional to the partial pressure of the
gas, temp. remaining constant Then: vapor pressure lowering
𝐶1 𝑃1
= ∆𝑃1 = 𝑃1 ° − 𝑃1
𝐶2 𝑃2
∆𝑃1 = 𝑃1 ° 𝑋2

2. Effect of temperature on the solubility

Solutions of Solids in Liquids
● Solubility of a gas over a given solvent decreases with
an increase in temperature therefore increase in Colligative Properties
kinetic energy • depend on the concentration (no. of particles) of solute
● Higher kinetic energy causes more motion in molecules or ions in solution but not on the chemical identity
molecules which break intermolecular bonds and of the solute
escape from solution.
1. Vapor Pressure lowering
3. Presence of dissolved substance on the solubility
● Presence of dissolved substance(electrolytes) lowers
the solubility of a gas.

Solutions of Liquids in Liquids

Raoult’s Law
• the vapor pressure of a component in a solution is directly
proportional to its mole fraction and is equal to the mole
fraction multiplied by the vapor pressure in the pure state at
that temperature

If: 𝑃1 = 𝑃1 ° (1 − 𝑋2 )
𝑃1 = 𝑃1 ° − 𝑃1 ° 𝑋2
𝑃1 ° − 𝑃1 = 𝑃1 ° 𝑋2

Then: vapor pressure lowering

The tendency of the two different sorts of molecules ∆𝑃1 = 𝑃1 ° − 𝑃1
to escape is unchanged. ∆𝑃1 = 𝑃1 ° 𝑋2

Phase diagram for Pure Water

P is pressure and X is mole fraction
P solvent in solution: 𝑃1 = 𝑃1 ° 𝑋1
P solute in solution: 𝑃2 = 𝑃2 ° 𝑋2
P solution: 𝑃𝑇 = 𝑃 𝑠𝑜𝑙𝑢𝑡𝑒 + 𝑃 𝑠𝑜𝑙𝑣𝑒𝑛𝑡
*if solute is non-volatile*
Therefore: 𝑷𝑻 = 𝑷𝟏 = 𝑷𝟏 ° 𝑿𝟏
𝑷𝟏 = 𝑷𝟏 ° 𝑿𝟏

2E-PH: Belmonte, Manalo, Sarto, Yan

Adding Solute to Water ❖ OSMOSIS
• Spontaneous process
• Diffusion of water across a semi-permeable membrane
• Semi-permeable membrane allows passage of solvent
but not solute
• Movement of solvent from lower solute concentration
to higher solute concentration
• Movement of solvent from higher solvent
concentration to lower solvent concentration

OSMOTIC PRESSURE
• Pressure required to stop osmosis
PV = nRT
BOILING POINT ELEVATION if P = Π and n/V = M
∆Tb α m then Π = MRT
∆Tb = kbm kb H2O = 0.51 Π = mRT

Kb Wsolute CRYOSCOPIC METHOD

∆Tb =
MWsolute x kgsolvent Π = mRT
ΔTf = kfm
∆Tb = Tb − Tb°
∆Tf
FREEZING POINT DEPRESSION m=
Kf
∆Tf α m ∆TfRT
∆Tf = kfm kf H2O = 1.86 Π=
Kf

Kf Wsolute *R = 0.0821 L-atm/n-K

∆Tf =
MWsolute x kgsolvent
Non-electrolytes Electrolytes
∆Tf = Tf° − Tf ΔP1 P1˚X2 iP1˚X2
ΔTb kbm ikbm
*Kb = ebullioscopic constant or molal boiling point constant ΔTf Kfm iKfm
*Kf = cryoscopic constant or molal freezing point constant Π mRT imRT
*i = dissociation or Van’t Hoff factor

Calculate the Dissociation Value (i)

1. KCl is a 2-ion electrolyte dissociating 80% in a certain
concentration. Calculate its dissociation value (i).

80 K+ ion
80 Cl- ion
20 undissociated particles

180 particles represent 1.8 times as many particles as there

were before dissociation, i = 1.8

2E-PH: Belmonte, Manalo, Sarto, Yan

 2. ZnCl2 is a 3-ion electrolyte dissociating 80% in a
certain concentration. Calculate its dissociation value
(i).

80 Zn+ ion
80 Cl- ion
80 Cl- ion
20 undissociated particles

260 particles represent 2.6 times as many particles as there

were before dissociation, i = 2.6

Non-electrolytes 1.0
Electrolyes (2-ion) 1.8
Electrolytes (3-ion) 2.6
Electrolytes (4-ion) 3.4
Electrolytes (5-ion) 4.2

2E-PH: Belmonte, Manalo, Sarto, Yan