This document discusses various distillation techniques used to separate mixtures. It defines distillation as the separation of constituents in a mixture including a liquid by partial vaporization and separate collection of the vapor. Simple distillation is used to purify liquids by heating the mixture until it vaporizes and condenses the vapor. Molecular distillation can distill normally non-volatile substances under high vacuum. Fractional distillation separates miscible liquids using their different boiling points over multiple equilibrium stages in a fractionating column. Azeotropic mixtures cannot be fully separated by distillation alone.

1. DISTILLATION
Dr: Fatehalrahman Magbool, PhD
Assist. Professor of Pharmaceutics
Department of Pharmaceutics
Al Neelain University

2. • Boiling point
• Temperature at which the pressure exerted by the surrounding upon a liquid is
equaled by pressure exerted by the vapour of the liquid.
• Under this condition addition of heat results in the transformation of the liquid
into it is vapour without raising the temperature.

3. • Distillation may be defined as the separation of the constituents of a mixture
including a liquid by partial vaporization of the mixture and separate collection of
the vapor.
• Such separations by distillation may include:
• a) Separation of one liquid from non-volatile impurities;
• b) Separation of one liquid from one or more other liquids, with which it may be
miscible, partially miscible or immiscible.
• As carried out in practice it is difficult to distinguish between evaporation,
distillation and drying, however, working definitions which serve to distinguish
the three processes; distillation is the operation used when the condensed vapor
is required; evaporation is used when the concentrated liquid residue is needed;
and drying has dried solid residue as product.

4. • The distillation operation is carried out on a large scale; simple distillation is
considered for the treatment of single liquids, with particular reference to
purification of water and the special techniques applied to materials such as fixed
oils.

5. • Simple Distillation
• The purification of many organic liquids is carried out by the simple distillation
process, and it is necessary to use only a simple apparatus with boiler and
condenser, so that equipment of the type described as evaporator can be used.
• As with evaporation, distillation process can be carried out under reduced
pressure if it is desirable to keep temperature as low as possible.

6. • Preparation of Purified Water and Water for injection by Distillation
• Purification of water by distillation is a special case, for the following reasons:
• gases dissolved in the raw water must be removed and not allowed to
contaminate the distillate; such gases include carbon dioxide but ammonia is
probably the most important gas to be avoided.
• The residue of solids must not be concentrated to a point where hydrolysis
occurs; otherwise the distillate may be contaminated by volatile materials e.g. by
hydrochloric acid from the hydrolysis of chlorides.
• These objectives may be achieved by using a batch distillation procedure and
collecting the middle fraction only. The use of purified water in pharmaceutical
practice is so great, however, that a continuous process is desirable.

7. • Molecular Distillation
• A special application of the simple distillation process is Molecular Distillation,
known also as Evaporative Distillation or Short-path Distillation.
• Theory of Molecular Distillation
• The Mean Free Path of a molecule is defined as the average distance through
which a molecule can move without coming into collision with another. The Mean
Free Path can be expressed mathematically as:
λ = η√(3/pρ)
where;
λ = mean free path; η = viscosity; p = pressure; ρ = density.

8. • For materials that are of low viscosity and density, the mean free path is long,
and distillation is simple. The mean free path is low for substances that are
viscous and at high pressure, but can be increased if the viscosity is decreased by
elevation of the temperature and the pressure is reduced.
• In this way, substances that are regarded as non-volatile under ordinary
conditions of temperature and pressure may become volatile. Hence, under
these conditions, with the evaporating surface close to the condensing surface it
is possible to distil such substances.

9. • Characteristics of the Molecular Distillation Process
• Compared with the simple distillation process used for volatile liquids, molecular
distillation has three characteristics:
• In order to minimize collisions between molecules, the process must be operated
under very high vacuum, usually of the order of 0.1 to 1N/m2 . This demands
efficient pumping systems, careful avoidance of leaks and precautions such as de-
gassing of the liquids prior to distillation.
• The liquid area should be as large as possible, there is no boiling, and evolution of
the vapor is from the surface only; this is why some times the title evaporative
distillation is used.
• The evaporating surface must be close to the condensing surface, accounting for
the occasional use of the title short path distillation.

10. • Usually, this distance is similar to the mean free path of the molecules to be
processed, although it can be somewhat greater, as it has been shown that the
molecules can withstand a number of collisions without appreciable deflection.

11. • Application of Molecular Distillation
• Although molecular distillation has applications for the purification of chemicals
of low vapor pressure, such as dimethyl phthalate, the most important
pharmaceutical use is for refining fixed oils and separating vitamins.
• This technique has been applied with great success to the purification of vitamin
A.
• For this purpose the fish liver oil is fed continuously as a thin film onto heated
discs rotating in a high vacuum.

12. • Fractional Distillation
• Theoretical Consideration and Small Scale Methods
• Fractional distillation is the process employed to separate miscible volatile liquids
having different boiling points.
• In a mixture of two liquids, each may be regarded as dissolved in the other and
the possibility of separating the two liquids by fractional distillation depends on
the effect each has on the vapour pressure of the other.

13. • Vapour Pressure of Miscible Liquids
• When the two components of a binary mixture are completely miscible, the
vapour pressure of the mixture is a function of the composition as well as the
vapour pressures of the two pure components.
• In an ideal solution where the relation of vapour pressure and composition is
given by Raoult's law, the partial vapour pressure of each volatile component is
equal to the vapour pressure of the pure component multiplied by its mole
fraction.
• Thus for a mixture of A and B:
PA = PA
O XA and PB = PB
O XB

14. • Fractional distillation is a mass transfer process, involving counter-current
diffusion of the components at each equilibrium stage.
• This can be represented by the concentration gradients so that the less volatile
component (LVC) diffuses through the boundary layers from the vapour to the
liquid phase, while the more volatile component (MVC) diffuses in the opposite
direction.
• Counter-current diffusion occurs, therefore, with the vapour becoming richer in
MVC and the liquid richer in LVC, until equilibrium is reached.
• This is repeated in a sufficient number of equilibrium stages until the vapour
consists entirely of the MVC and the liquid is the LVC.

15. • Azeotropic mixtures
• An Azeotropic mixture or constant boiling mixture is one in which the
composition of the liquid and the vapour in equilibrium with it is the same. Thus
the mixture behaves like a pure liquid in so far as it distils without change in
composition or boiling point.
• Such mixtures cannot be separated into their pure components by distillation. It
is possible to separate them by distillation only into one component and a
constant boiling mixture.
• The influence of azeotropes and the manner in which they can be used are
illustrated by the methods used for the preparation of absolute alcohol.
• The liquor from fermentation processes is a common source of ethanol and
contains approximately 8 to 10 per cent; purification is by distillation, forming an
azeotrope containing 95.6 per cent ethanol and boiling at 78.15°C at atmospheric
pressure. From which water can be taken in further processes to obtain absolute
water.

16. • Fractionating Columns
• If a mixture of chloroform, boiling point 61.2o and benzene, boiling point 80.2o, is
distilled, the vapours first evolved will be richer in the more volatile component,
chloroform; as this is distilled off, the vapours will become gradually richer in
benzene, and the temperature of distillation will gradually rise.
• By changing the receiver when the temperature has risen from 61 to 63 a fraction
is obtained which is richer in chloroform than in benzene.
• Other fractions, which are increasingly rich in benzene, may be collected over the
ranges 63 to 68°, 68 to 73°, 73 to 78°, 78 to 80o.

17. • Repeated separate distillations of the intermediate fractions, fractions of the
same boiling range being combined, will ultimately result in a separation of the
liquid into two main fractions, boiling point 61' to 63 and 78° to 80 which
represent a rough separation of the two constituents of the mixture.
• This process is very tedious and the same, or a better effect can be achieved in a
single distillation through a fractionating column, which is inserted between the
still and the condenser, and acts by bringing about repeated distillations
throughout the length of the column.

18. THANKS