Colligative properties

Colligative properties: physical properties of solutions that depend on the number but not the type of solute particles.

Four (4) important colligative properties:

1. Vapor-pressure lowering 2. Boiling point elevation: Boiling point of a solution is higher than that of the pure solvent 3. Freezing point depression: Freezing point of a solution is lower than that of the pure solvent 4. Osmotic pressure

Lowering of vapor pressure and Boiling Point Elevation

What is the boiling point of a liquid?
It is the temperature at which the vapor pressure equals the atmospheric pressure. So

if you decrease the vapor pressure, you must increase the boiling

point it will take a higher temperature to get enough gas

molecules (vapor pressure) to equal the atmospheric pressure.

Non-volatile solutes and Raoults law

Vapor pressure of solvent in solution containing non-volatile solute is always lower than vapor pressure of pure solvent at same T At equilibrium, rate of vaporization = rate of condensation

Solute particles occupy volume reducing rate of evaporation

the number of solvent molecules at the surface The rate of evaporation decreases and so the vapor pressure above the solution must decrease to recover the equilibrium

Boiling point elevation

Boiling Point Elevation Equation

Tb = Kbm Tb = boiling point elevation Kb = molal boiling point elevation constant (these values change depending on the solvent) m = molality

Freezing point depression

Freezing involves the congregation of solvent particles as temperature is lowered

So in a solution, solvent molecules freeze first

In the solution solute particles are located between the solvent particles - so a lower temperature is needed to freeze the solution Tf = Kf m Tf = freezing point depression Kf = molal freezing point depression constant m = molality

Osmotic Pressure
Whenever a solution is separated from a solvent by a membrane that is only permeable to solvent molecules (referred to as a semipermeable membrane), there is a passage of solvent across the membrane into the solution. This is the phenomenon of osmosis. Osmotic pressure is the pressure required to overcome the natural

pressure exerted by a solution by virtue of having a concentration.

The equation which relates the osmotic pressure of the solution, to the solution concentration is the van't Hoff equation:

V = n2RT
where V is the molar volume of the solute and n2 is the number of moles of solute.

Osmotic Pressure
Osmotic pressure is a colligative property, which means that its value depends on the number of ions in solution.

Therefore, if the drug is ionized you need to include the

contribution of the counter ions to the total number of ions in solution.

Importance of Osmotic pressure for us?

Because the red blood cell membrane acts as a semipermeable membrane it is important to ensure that the osmotic pressure of solutions for injection is approximately the same as that of blood serum. Such solutions are said to be isotonic with blood. Solutions with a higher osmotic pressure are hypertonic and those with a lower osmotic pressure are termed hypotonic solutions.

Similarly, in order to avoid discomfort on administration of

solutions to the delicate membranes of the body, such as the eyes, these solutions are made isotonic with the relevant tissues.

Osmotic pressure
Osmotic pressure is not a readily measurable quantity and it is usual to use the freezing-point depression (which is also a

colligative property) when calculating the quantities required to

make a solution isotonic. A solution which is isotonic with blood has a freezing-point depression, Tf, of 0.52C. Therefore the freezing point of the drug solution has to be adjusted to this value by adding sodium chloride

to make the solution isotonic.

Making a solution isotonic

The amount of the adjusting substance required can be calculated from: w = (0.52a)/b where w is the weight in grams of adjusting substance to be added

to 100 cm3 of drug solution to achieve isotonicity,

a is the number of grams of drug in 100 ml of solution multiplied by Tf of a 1% drug solution, b is Tf of 1% adjusting substance.

Determination of molecular mass from colligative properties

1. From Vapor Pressure lowering Raoults Law equn. P*pure - P*solution = X* P*pure P*pure - P*solution = n = w/m P*pure n+N w/m + W/M w & m = Weight and molecular mass of solute W& M = Weight and molecular mass of solvent For very dilute solutions, w/m is negligibly small Therefore, P*pure - P*solution P*pure = wM mW

2. From Boiling point elevation

Elevation in boiling pt. lowering in vapor pressure
T (P-Ps) / P Using Raoults Law from dilute solutions, (P-Ps) / P wM / Wm M is constant, Therefore, (P-Ps) / P w / Wm

Combining the above to equation,

T w / Wm T = Kb*(w/m)*(1/W) If w/m = 1, W= 1kg (1000g), Kb = T Kb = RTb2 / 1000*Lv

3. From Freezing point depression

T = Kf*(w/m)*(1/W) Kf = RTf2 / 1000*Lf

4. From Osmotic pressure

Using Vant Hoff Equation, V = n RT V = (w/m) RT

m = w RT/ V

Measurement of Colligative properties

1. Measurement of lowering of vapor pressure a) Barometric method: Separately measures the vapor pressure

of pure solvent and solution using the depression in mercury

level in a barometer tube.
Its not accurate because the lowering in vapor pressure is very small.

b) Manometric method:

c) Ostwald and walkers dynamic method: Gas Saturation method.

Ostwald and walkers dynamic method

arrangement to calculate relative lowering in vapor pressure. In this method, a stream of dry air is bubbled successively through (i) the solution (ii) the solvent and (iii) a reagent which can absorb the vapors of the solvent. Generally solvent is water and reagent is anhydrous CaCl2. All the bulbs must be kept at the same temperature and air must be bubbled gradually to ensure that it gets saturated with the vapors in each bulb. The dry air, as it passes through the solution, takes up an amount of vapour which is proportional to the vapor pressure of the solution at the prevailing temperature. This moist air passes through water (solvent), it takes up a further amount of vapor

which is proportional to the difference in vapor pressure of pure solvent and the
solution.

 If W1 and W2 be the loss of weight in Set in solution and solvent bulb resp. W1 Ps
(1) (2)

W2

P-Ps
Ps + P-Ps P

(1) + (2)W1 + W2 W1 + W2 (2)/(3).P-Ps / P =

(3)

W2/ W1 + W2

Landsberger-Walker method
T = Thermometer

A = Vessel
B = Delivery tube C = Hole D = Outer Vessel E = Side tube

F = Flask

Cottrells Method
The diagram, fig. 1, shows a boiling tube, whose narrowed upper portion itself serves as condenser tube. A glass cylinder, open above and

below and of diameter slightly less

than the boiling tube itself, is located concentrically within the latter, and confers the advantages of a double jacket.

Cottrells Method
Within this is supported the differential thermometer, on the lower bulb of which hangs the pump, loosely, as a hat on a peg.

The boiling tube is heated by a common Bunsen burner, with a low flame
protected by the customary metal draught shield. When boiling begins, portions of the liquid in the bulb are carried by the vapor in fragments up the pump and discharged to form a thin film over the lower bulb of the thermometer, which thus attains the temperature

at which this liquid, or solution, is in equilibrium with the vapor.

The upper bulb acquires the temperature of the pure boiling solvent. The thermometer registers the difference between these two temperatures.

Measurement of freezing point depression

Beckmans method

2. Rast Camphor Method

Pure camphor is used as a solvent.
Fill a little pure camphor into a capillary with one end sealed. The tube is now attached to a thermometer with a rubber band. The assembly is put into a thiele tube full of oil. Record the melting point of the pure solvent (camphor). Measure the mass of an empty test tube. Add about 1 gram of amphor and record its mass. Add about 0.1 gram of the unknown

solute and record its mass.

The contents of the test tube are melted by placing it in an oil bath preciously heated.

 The tube is taken from the bath, propped up in another beaker and allowed to cool. Some of the solid is scraped from the tube and

powdered on a watch glass.

A little of the solid is put into a melting point tube as before. The tube is attached to the thermometer and the melting point is obtained. Record the melting point of the mixture.

Partition Coefficient
A measure of a drugs lipophilicity and an indication of its ability to cross cell membranes. It is defined as the ratio of unionized drug distributed between the organic and aqueous phases at equilibrium. P o/w = (C oil / C water) equilibrium For series of compounds, the partition coefficient can provide an

empiric handle in screening for some biologic properties.

Octanol is usually used as the non-aqueous phase in experiments to measure the partition coefficient of drugs. Other non-aqueous solvents, for example isobutanol and hexane, have also been used.

Partition Coefficient
If two immiscible phases are placed in contact, one containing a solute soluble to some extent in both phases, the solute will distribute itself until the chemical potential of the solute in one phase is equal to its chemical potential in the other phase.

Partition coefficient has been shown to be a contributing factor for

the rate and extent of drug absorption. Since biological membranes are lipoidal in nature. The rate of drug transfer for passively absorbed drugs is directly related to the lipophilicity of the molecule.

Partition Coefficient
Examples of partitioning include: drugs partitioning between aqueous phases and lipid biophases. preservative molecules in emulsions partitioning between the aqueous and oil phases.

antibiotics partitioning into microorganisms.

drugs and preservative molecules partitioning into the plastic of

containers or giving sets.

Determination of Partition coefficient; logP

Shake flask (or tube) method

HPLC determination
Electrochemical methods

Physiochemical properties of drugs

Determining logP
In drug discovery and development, lipophilicity is usually expressed by the partition between water and octan-1-ol. The partition coefficient, P, of a drug is given by:
D

where [drug molecule]o = concentration of drug in octan-1-ol [drug molecules]w = concentration of drug in water

drug moleculeo drug moleculew

Where, [drug molecule]o = concentration of drug in its molecular form in octan-1-ol; [drug molecule]w = concentration of drug in its molecular form in water; [drug ion]w = concentration of drug in its ionised form in water. The distribution constant depends on pH. A plot of pH against logD gives a curve with a horizontal section at lower pH values. In this range, distribution is not pH dependent and logD = logP.

drug moleculeo drug moleculew drug ionw

In the traditional shake flask method, a sample of the drug is shaken with a octan-1-ol/water mixture and its concentration in each layer is determined. Drugs that ionise in water
The situation is more complex with drugs that ionise in aqueous solution and that is most of them. These drugs are characterised by their distribution constant, D. Its value depends on pH. Determining logD at various pHs allows logP to be calculated.