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85
Unit Operations
should be less. This is to prevent the pores of the filter medium
from clogging or plugging, which subsequently increases
resistance to the flow. Thus Kozeny-Carman equation results
which is expressed as:
V
A
S
P
KL
=
∆
−η
ε
ε
2
3
2
1
()
Where,
A = Area of filter medium
S = Specific surface area of the particles comprising the
cake (m
2
/m
3
)
DP = Pressure drop across the filter medium and the filter cake
K = Kozeny constant
e = Porosity of the cake (bed)
Since the flow rate and
ε
ε
3
2
1
()
−
are directly proportional,
10%
change in porosity can change V up to 3 folds.
MEMBRANE FILTERS
Seitz Filter
Seitz filter was developed in Germany and marketed under
the trade name Seitz. They are usually round but occasionally
square. These filters consist of two parts. The lower part is
fitted with a perfoated plate over which a compressed asbestos
pad is placed which acts as a filtering media. The asbestos
filter pads are made in several porosities out of which grade
EK is used for bacterial filteration. The upper part has a valve
through which pressure can be applied. The two parts, i.e.
upper and lower are joined together by means of winged nuts
(Fig. 4.13). The solution to be filtered is filled in the apparatus,
pressure is applied through the valve and filtered solution is
collected at the bottom in sterilized containers.
Advantages
As the pads are meant for single use, a new pad is to be
used each time and there is no risk of contaminating the
filtrate.
Introduction to Pharmaceutics
86
The apparatus is very simple to use.
For viscous solutions they are more suitable than ceramic
or glass filters.
Disadvantages
Asbestos pads may shed loose fibres which makes the
solutions unsuitable for injections.
It imparts alkalinity to the filtrate which may be sufficient
to precipitate the alkaloids from solutions of their salts.
The pads may adsorb sufficient amount of medicament
which may result in loss of volume specially when the
quantity of solution is small.
Sintered Glass Filters
Sintered glass filters consist of ground glass particles which
are fused together by heating to its sintering point (it is that
temperature at which the glass particles are fused together
to become solid, without melting). The fused partices have
intersticses between themselves which form a suitable system
for filtration. They are prepared in the from of discs of suitable
size and shape which are then sealed by heat into a Pyrex glass
funnel, having the shape of buchner funnel. These so fused
funnels are known as sintered glass funnels, which are made
Fig. 4.13: Seitz filter.
87
Unit Operations
in several porosities (Fig. 4.14). For bacterial filtration grade 5
having the maximum pore size of 2 µm is used, for clarification
of solutions filters with other porosities are used.
These filters are very fragile, so must be handled carefully.
After use they must be cleaned thoroughly. For cleaning they
must be washed by suction with hot hydrochloric acid and
then with distilled water, until the medium is free from acid.
Advantages
If properly cleaned, nothing can enter into the filtrate, there-
fore, they are generally used for the filtration of solutions to
be injected.
They are useful for filtering small as well as large volumes.
Very little amount of medicament may be absorbed.
Volume of filtrate retained in the medium is negligible.
Disadvantages
They are very costly.
The medium is unsuitable for large volume filtration
because for this purpose large discs are required which are
mechanically weak.
Berkefeld Filters
Berkefeld filters are test tube shaped filters called “filter
candles” or “ceramic candles”. They are made up of unglazed
porcelain or kieselguhr and are available in various porosity
Fig. 4.14: Sintered glass filter.
Introduction to Pharmaceutics
88
grades. They are hollow cylinders mounted on metallic joints.
One end of the candle is closed and the other is fitted with a
narrow opening which is attached to a vacuum pump at the
time of its use. These candles can be sterilized by moist heat
sterilization at 121°C for 20 minutes.
For filtration, the candle is placed in the solution to be
sterilized. The narrow opening is attached to the vacuum pump.
When the vacuum is applied and pressure inside the candle
is decreased, the solution is forced to move inside the candle
from where it is collected in large size sterilized containers. The
solution so filtered is distributed in final containers which are
sealed immediately. The whole process of filtration is carried
out under strict aseptic conditions (Fig. 4.15).
By the repeated use of filtration candles, they may get
clogged and can be easily cleaned by scrubbing the outer
surface of the filter with a brush and passing the water under
pressure from inside to outside direction which will remove
the entangled particles from the interstices.
Advantages
Themolabile solutions can be sterilzed without undergoing
any change.
All, living as well as dead microorganisms are removed.
Fig. 4.15: Berkefeld filter
89
Unit Operations
Disadvantages
The main disadvantage of such filters is that the pores get
blocked which require thorough cleaning before the process
is repeated.
As compared to other filtration medias these candles are
little difficult to fit into the filtration units.
Millipore Filters
They are porous structures made up of pure and biologically inert
cellulose ester. These filters posses high degree of uniform pore
size, high flow and high thermal stability. They do not absorb
the solution and are resistant to chemicals. Millipore filters are
available in pore size ranging from a high of 8 μ to a low of
0.01 μ. Generally a grade with pore size of 0.22 ± 0.02 μ is used
for bacterial filtration. Among the various bacterial filters
available, the millipore filters are the most suitable effective
method. Small volumes and large volumes of solutions can be
filtered easily.
Membrane Filters
Membrane filters have become very common among
ultrafiltration methods because the membranes used have
been refined to a great extent They are made up of cellulose,
polyvinyl chloride, nylon and other cellulose derivatives. They
are very fine having a wide range of pore size from 8 μ down
to 0.22 μ. However, for bacterial filtration, membranes with
pore size of 0.22 to 0.45 μ are recommended. For use these
membranes are fixed in a funnel of desired size and shape as is
done in the case of sintered glass funnels.
Advantages
Bacteria are removed by sieving.
Because the membranes used are very thin therefore
adsorption of medicament is negligible.
A new disc is used for every new operation.
Filtration is quite rapid.
They do not liberate particles or chemical substances to the
filtrate.
Introduction to Pharmaceutics
90
Disadvantages
Fine pores may get clogged easily for which a prefilter may
be used to remove colloidal matter. ·
Chemically they are less reistant and are soluble in certain
organic solvents, e.g. ketones and esters.
They are very brittle when dry and in this condition they
can be stored for years together.
Membrane filters are extensively used for filtration and
steri lization of a large number of pharmaceutical preparations
such as parenteral preparations, ophthalmic solutions, bio-
logical preparations, hormones and enzymes. They are equally
suitable for use in hospitals and in industries.
DRYING
DEFINITION
Drying is an important process in almost all the pharmaceutical
industries. There is hardly any pharmaceutical plant engaged
in the manufacture of tablets or capsules that does not use
dryers. Drying is commonly the last stage of the process before
packaging and has a considerable effect on the properties of
the product which may prevent the deterioration, produce a
readily soluble or free flowing·product.
Drying is defined as a process in which the liquid is removed
from a material by the application of heat and is accomplished
by the transfer of a liquid from a surface into an unsaturated
vapour phase. Drying is needed for the following purposes:
For the preparation of granules which can be dispensed in
bulk, compressed in the form of tablets or filled in capsules.
For the preparation of certain products like dried aluminium
hydroxide, spray dried lactose and powdered extracts.
For reducing the bulk and weight, thereby lowering the
cost of transportation and storage.
Vegetable drugs are dried before extraction to facilitate
grinding and to avoid deterioration on storage.
As dried products are more stable than moist ones,
therefore, heat is required for drying.
91
Unit Operations
Various methods and equipment for drying are available
the choice of which depends on the following factors:
Whether the product is sensitive to heat or not.
Physical characteristics of the product before drying.
The nature of the solvent to be removed.
Whether the process is to be carried out under aseptic
conditions or not.
Quantity of the product to be dried.
Available source of beat
Cost involved.
Types of dryers:
Fluidized bed dryer.
Freeze drying.
Fluidised Bed Dryer
Fluidised bed dryer is known by the name because a gas is
allowed to flow upward through a bed of particulate solids at
a velocity greater than the settling velocity of the particles, the
solids will be blown up and become partially suspended in the
gas stream (Fig. 4.16). The resultant mixture of solids and gas
behaves like a liquid and the solids are said to be fluidised.
This technique is very efficient and is used for drying granular
solids because each particle is surrounded by the drying gas.
Two types of fluidised bed dryers are used in pharmaceutical
industries, i.e. vertical and horizontal. The vertical type is
used for batch drying whereas horizontal type is used for
continuous drying. A typical vertical fluidised bed dryer for
pharmaceutical use is shown in Fig. 4.16.
It consists of stainless steel chamber with a perforated
bottom, into which the wet material to be dried is placed. For
loading and unloading the drying chamber is removed from
the unit. The air is introduced from below which is 200 heated
by means of heaters fitted therein, filtered and then passes
through the powder bed by means of induction fan fitted in the
upper part of the apparatus. The air is heated to the required
temperature and its flow rate is adjusted. As the velocity of the
air is increased the bed begins to expand. Further increase in
Introduction to Pharmaceutics
92
velocity beyond this point will cause rapid expansion of the bed
and particles begin to show a turbulent motion “fluidisation”.
The particles are not in direct contact with each other and
efficient heat exchange takes place between the particles and
the flowing air. The moist air is carried away rapidly. With
these types of dryers materials ranging from 5 to 200 kg can be
dried in about 20 to 40 minutes compared with 24 hours cycle
in conventional tray dryers.
Advantages
They are efficient as material can be dried within 20 to
40 minutes compared with several hours in tray dryers.
Drying takes place from individual particles and not from
whole bed.
The temperature of a fluidised bed is uniform and can be
controlled to the desired temperature.
A free flowing product is produced.
Fig. 4.16: Fluidized bed dryer
93
Unit Operations
Since the containers are mobile which make handling easy
thereby labour costs are reduced.
Due to short drying time the unit has a high output.
Disadvantages
Due to turbulence of the fluidised state, large quantities of
fines are produced but the use of suitable binders during
granulation can overcome this defect.
Too wet granules stick together on drying therefore too wet
granules must not be used.
Many organic powders develop electrostatic charges
during fluidisation so efficient electrical earthing of the
drying chamber and the cloth filters is necessary.
Fluidised bed drier can be used for drying any powdered
material but has special application in drying the tablet
granules and is widely used for this purpose.
Freeze Drying
Freeze drying is the process in which water is removed from
liquid products by sublimation hence this process is also known
as sublimation drying. As the dried product has great affinity
for water (lyophilic-liquid loving), therefore, this process is also
known as lyophilization. In this process the liquid is first frozen
to ice before application of vacuum, to avoid frothing then
sublimation of frozen ice is carried out under reduced pressure.
The vaporization of ice occurs only at the surface hence the
frozen ice is exposed to large surface area for rapid sublimation
(Fig. 4.17).
Freeze drying on large scale may be carried out by freezing
the product in a container kept on the shelf of a chamber by
circulating a refrigerant like freon, ammonia or ethylene glycol
from the compressor through the pipes fitted along the sides
of the shelf. When the freezing is complete, vacuum is applied
to the chamber which has been previously chilled by means of
circulating the refrigerant from the large compressor.
Heat is then supplied to the product by heating coils or by
circulating hot water. The process is continued till the product
is dry and a spongy solid material is left behind.
Introduction to Pharmaceutics
94
The liquid products to be freeze dried are sterilized and
distributed aseptically to the final containers which are kept
open during the drying process and are immediately sealed as
soon as the drying is complete.
Applications
Freeze drying is used for the manufacture of certain pharma-
ceutical and biological products which are thermolabile.
It is also used for drying blood plasma, vitamins, enzymes,
hormones and antibiotics.
Freeze dried product has definite physical properties as
compared to products dried by other methods. Freeze-dried
products are more stable than vacuum dried products and are
often more readily soluble.
Since freeze-drying is very slow and expensive process it is
preferably used for those products which cannot be dried by
any other method.
Fig. 4.17: Freezing dryer