Pharmaceutical engineering - Textnotes

Centrifugation
Syllabus: Objectives, principle & applications of centrifugation, Principles, construction, working,
uses, merits and demerits of Perforated basket centrifuge, Non-perforated basket centrifuge, semi
continuous centrifuge & super centrifuge.

• Centrifugation is a unit operation employed for separating the constituents present in a dispersion
with the aid of centrifugal force.
• Centrifugal force provides the driving force for the separation.
• Centrifugal separation is faster compared to filtration (gravity). The degree of separation if high,
because the forces applied are of high order of magnitude. In short, centrifugation provides a
convenient analytical method of separating either two immiscible liquids or a solid from a liquid
(biochemical or microbiological). The equipment used for the separation are known as centrifuges.
Process of Centrifugation
• The centrifuge consists of essentially a container in which a mixture of solid and liquid or two liquids
is placed and rotated at high speeds. The
• Mixture is separated into its constituent parts by the action of centrifugal force on their densities. A
solid or liquid of higher specific gravity is thrown outward with greater force. Therefore, it is retained
at the bottom of the container leaving a clear supernatant layer of pure liquid.
• The speed of a centrifuge is commonly expressed in terms of the number of rotations per minute of
the rotor.
Applications
1. Production of bulk drugs: Centrifugation technique is used to separate crystalline drugs such as
aspirin from the mother liquor. Free flowing product results due to the removal of traces of mother
liquor and avoidance of effervescence.
2. Production of biological products: Most of the proteinaceous drugs and macromolecules are
present as colloidal dispersion in water. By normal separation methods, it is difficult to produce
them in large scale. Centrifugal methods are used for the separation of these constituents from
water. Insulin can be obtained in pure form by selectively precipitating other fractions of proteins
and subsequently separating them by ultracentrifugation. Centrifugation is employed for separating
the blood cells from blood.
3. Biopharmaceutical analysis of drugs: Drugs present in the blood, tissue fluids and urine are
normally present in the form of colloidal dispersions. Centrifugation is used for separating the drugs.
4. Evaluation of suspensions and emulsions: Centrifugation method is used as a rapid empirical test
parameter for the evaluation of suspensions and emulsions. Normally, creaming is slow process in
emulsions. This process can be hastened by inducing stress condition (using a centrifuge). A stable
emulsion should not show any signs of separation even after centrifuging at 2000-3000 rotations
per minute at room temperature.
5. Determination of molecular weight of colloids: Determination of molecular weight of a polymer is
not possible by usual methods. Ultracentrifugation methods are used for determination of
molecular weight of serum albumin, insulin and methylcellulose. Centrifugation
(ultracentrifugation) is also used for ascertaining the degree of homogeneity of the sample.

Centrifugation
Pharmaceutical engineering - Textnotes
Classification of centrifuges
❖ Classification based on their mechanisms of separation.
1. Sedimentation Centrifuge
• Sedimentation centrifuge is a centrifuge that produces sedimentation of solids based on the
difference in the densities of two or more phases of the mixture. The efficiency depends on the
velocity of rotation to which the mixture is subjected. E.g. horizontal continuous centrifuge,
supercentrifuge and conical disc centrifuge.
• Ultracentrifugation: When extremely fine solid matter is to be separated from a liquid for example in
colloidal research, ultracentrifuge is used. In this instrument, a relatively small rotor is operated at
speeds exceeding 1,00,000 rotations per minute and with forces up to one million times gravity.
• Centrifuges have replaced the gravity separators to a considerable ex- tent in production operations
because of their effectiveness in separation.
✓ Uses:
(1) Suspensions containing low concentration of solids can be separated quickly.
(2) Lanolin is recovered from the wool by scouring process.
(3) Olive and fish liver oils are purified by removing dirt and water.
(4) The liquid/liquid phases are separated in the extraction of drugs, for example, manufacture of
antibiotics.
(5) Bacterial enzymes are prepared by removing bacteria..
(6) Blood plasma is separated from whole blood.
(7) Starch is collected after washing and purification stages.
(8) In the manufacture of insulin, liquor is clarified so as to remove the precipitated proteins.
✓ Advantages:
(1) Centrifuges are compact and occupy a very small space.
(2) The separating efficiency is very high, so that the particles are deposited very rapidly. It is
suitable, if the sediment is a fluid deposit or sludge.
(3) Two immiscible liquids are easily separated on a continuous process.
(4) By controlling the speed of rotation and rate of flow, coarse particles are separated, while finer
particles remain in the suspension.
✓ Disadvantages:
(1) The construction of sedimentation centrifuges is complicated.
(2) Its capacity is limited.
2. Filtration Centrifuge
• Filtration centrifuge is a centrifuge in which solids pass are retained by porous medium allowing
liquid to rush out due to centrifugal effect.
• In this type the container contains a porous wall through which the liquid phase may pass and on
which the solid phase is retained. E.g. are perforated basket centrifuge and semi-continuous
centrifuge. The solids that form a porous cake can be separated in the filtration centrifuge. Normally
perforated wall such as canvas or metal cloth is covered with a filter medium.
✓ Uses:
(1) When solid recovery is the primary goal, centrifugation must be considered as an alternative to
simple filtration.

Centrifugation
Pharmaceutical engineering - Textnotes
(2) It is also used for removing unwanted solids from a liquid. For example, precipitated proteins are
removed from insulin.
✓ Advantages:
(1) It can handle slurries with a high proportion of solids and even those having paste like
consistency.
(2) The final product has very low moisture content.
(3) The dissolved solids are separated from the cake.
✓ Disadvantages:
(1) The entire cycle is complicated resulting in considerable labour costs.
(2) It is a batch process or semi-continuous type.
(3) The solids may form a hard cake, due to the centrifugal force, which is difficult to remove.
➢ Classification Based on Scale of Usage
o Laboratory scale: Horizontal spinning arm type, Angle centrifuge (45 to 50 angle), High speed
centrifuge (10,000 rotations per minute), Ultracentrifuge (85,000 rotations per minute)
o Commercial scale:
▪ Batch type: Perforated basket centrifuge
▪ Semi-continuous scale: Short-cycle batch centrifuge
▪ Continuous centrifuge: Supercentrifuge

Perforated Basket Centrifuge

• In this centrifuge, a basket is mounted above a driving shaft. Such an arrangement is described as
under-driven. Conversely, if the basket is suspended from a shaft, it is described as over-driven.
These are used for batch processes. An under-driven bowl centrifuge is described below,

✓ Principle: Perforated basket (bowl) centrifuge is a filtration centrifuge. The separation is through a
perforated wall based on the difference in the densities of solid and liquid phases. The bowl
contains a perforated side-wall. During centrifugation, the liquid phase passes through the
perforated wall, while solid phase is retained in the bowl. The solid is removed after cutting the
sediment by a blade when the centrifuge stops.
✓ Construction: The construction of a under-driven perforated basket centrifuge is shown in Figure
11-5. It consists of a basket, made of steel (sometimes covered with vulcanite or lead) or copper or
monel or any other suitable metal. The basket material of construction should be such that it offers
Centrifugation
Pharmaceutical engineering - Textnotes
the greatest resistance to corrosion. The basket may have a diameter of 0.90 m and a capacity of
0.085 m³. The diameter of the perforations should be selected based on the size of crystals to be
separated. In case, the size of perforations is bigger than that of the particles, a filter cloth is
employed. The basket is suspended on vertical shaft and is driven by a motor using suitable power
systems such as belt pulleys, water turbines and electric motors. The basket may require about 5
kilowatt power for starting and 2 kilowatt power for running. Sometimes, steel hoops are used
externally to strengthen the basket. Surrounding the basket, a casing (stationary) is provided which
collects the filtrate and discharges it at the outlet.
✓ Working: The material (feed) is kept in the basket when the basket is stationary. The amount of
material should be optimum, otherwise, during centrifugation it puts a great strain on the basket.
The loading of material must be done to give even distribution. Power is applied to rotate the basket
and maximum speed must be attained quickly. The basket runs at 1000 rotations per minute. The
power required for running is small compared to the power required for starting and bringing it to the
full speed. During centrifugation, the liquid passes through the perforated wall, while the solid
phase retains in the basket. The liquid leaves the basket and is collected at the outlet. The cake is
then spun to dry as much as possible. Sometimes higher speeds are used so that the cake will be
completely dried. After a definite period of time, the power is turned off. By applying a brake the
centrifuge is stopped. The basket is brought to rest. The solid cake is cut using a blade and then
unloaded manually.
✓ Uses:
(1) Perforated basket centrifuge is extensively used for separating crystalline drugs (such as aspirin)
from the mother liquor. Free flowing product can be obtained because mother liquor is removed
completely.
(2) It is also used for removing unwanted solids from a liquid. For example, precipitated proteins are
removed from insulin.
(3) Sugar crystals are separated using perforated basket centrifuge.
✓ Advantages:
(1) The centrifuge is very compact and it occupies very little floor space.
(2) It can handle slurries with a high proportion of solids and even those having paste like
consistency.
(3) The final product has very low moisture content.
(4) In this method, the dissolved solids are separated from the cake.
(5) The process is rapid.
✓ Disadvantages:
(1) The entire cycle is complicated resulting in considerable labour costs.
(2) It is a batch process.
(3) If the machine is adapted for prolonged operation, there is considerable wear and tear of the
equipment. On prolonged operation, the solids may form hard cake, due to the centrifugal force,
which is difficult to remove simultaneously.

Non-perforated Basket Centrifuge

✓ Principle: This is a sedimentation centrifuge. The separation is based on the difference in the
densities of solid and liquid phases without a porous barrier. The bowl contains a non-perforated

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Pharmaceutical engineering - Textnotes
side-wall. During centrifugation, solid phase is retained on the sides of the basket, while the liquid
remains at the top, which is removed by a skimming tube.
✓ Construction: The construction of a under-driven non-perforated basket centrifuge is shown in
Figure 11-6. It consists of a basket, which may be made of steel or any other suitable metal. The
basket is suspended on vertical shaft and is driven by a motor using a suitable power system.

✓ Working: The suspension is fed continuously into the basket. During centrifugation, solid phase is
retained on the sides of the basket, while liquid remains on the top. The liquid is removed over a weir
or through a skimming tube (Figure 11-6). When a suitable depth of solids has been deposited on
the walls of the basket, the operation is stopped. The solids are then scraped off by hand or using a
scraper blade.
✓ Uses: Non-perforated basket centrifuge is useful when the deposited solids offer high resistance to
the flow of liquid.

Semi-continuous centrifuge or Short Cycle Automatic Batch Centrifuge

✓ Principle: Semi-continuous centrifuge is a filtration centrifuge. The separation is through a

perforated wall based on the difference in the densities of solid and liquid phases. The bowl
contains a perforated side-wall. During centrifugation, the liquid phase passes through the
perforated wall, while solid phase retains in the bowl. The solid is washed and removed by cutting
the sediment using a blade. It is a short cycle automatic batch centrifuge.
✓ Construction: The construction of a semi-continuous centrifuge is shown in Figure 11-7. It consists
of a vertical perforated basket, which is supported from a horizontal shaft driven by a motor. From
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Pharmaceutical engineering - Textnotes
the open side of the basket, provisions are made at the centre to introduce feed and wash pipe
through horizontal tubes. A feeler (not shown) rides over the feed, which is connected to diaphragm
valve through air supply. The feeler controls the thickness of the feed. Hydraulic cylinder attachment
is made in such a manner that the discharge chute enters from the sides of basket, when discharge
of crystals is desirable.
✓ Working: The perforated basket is allowed to rotate and slurry is introduced from the side pipe.
During centrifugation, the slurry passes through the perforated wall. The solids are retained in the
basket, while filtrate leaves the basket, which is collected at outlet. Further, the cake is washed with
water. The wash escapes from the basket through the filtrate outlet. After achieving the desired
thickness (50 to 70 mm), the feeler cuts off the air supply to a diaphragm valve that automatically
shuts off the entry of slurry. The hydraulic cylinder is actuated, which lifts the knife along with the
discharge chute. The knife does not cut the cake completely down to the screen, but leaves a layer
of crystals that acts as a filter medium for further separation in the next cycle. The residual crystals
may be given a brief wash before starting the next cycle. Through a timer and air supply
mechanisms, diaphragm valves controls all steps. Therefore, the entire cycle is semiautomatic. The
discharged crystals may contain 2 to 4% of moisture.
✓ Advantages: Short-cycle automatic batch centrifuge is used when solids can be drained fast from
the bowl.
✓ Disadvantage: During discharge, considerable breakage of crystals is possible. Many moving parts
are involved making the construction and functioning more complicated.

Supercentrifuge
• Sharples supercentrifuge is a continuous centrifuge used for separating two immiscible liquid
phases.
✓ Principle: Supercentrifuge is a sedimentation centrifuge. The separation is based on the difference
in the densities between two immiscible liquids. Centrifugation is done in the bowl of small
centrifuge. During centrifugation, the heavier liquid is thrown against the wall, while the lighter liquid
remains as an inner layer. The two layers are simultaneously separated using modified weirs.
✓ Construction The construction of a supercentrifuge is shown in Figure 11-9. It consists of a long
hollow cylindrical bowl of small diameter. It is suspended from a flexible spindle at the top and
guided at the bottom by loose-fit bushing. It can be rotated on its longitudinal axis. Provision is made
at the bottom for the feed inlet using pressure system. Two liquid outlets are provided at different
heights at the top of the bowl, and modified weirs, are attached.
✓ Working: The centrifuge is allowed to rotate on its longitudinal axis at a high speed, usually about
2000 revolutions per minute with the help of drive-assembly. The feed is introduced from the bottom
of the centrifuge using a pressure system. During centrifugation, two liquid phases separate based
on the difference in their densities. The heavier liquid is thrown against the wall, while the lighter
liquid forms an inner layer. Both liquids rise to the top of the vertical bowl. The liquid-liquid interface
(the so-called neutral zone) is maintained by an hydraulic balance. These two layers are
simultaneously removed as two liquids separately from different heights through modified weirs (as

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Pharmaceutical engineering - Textnotes
shown in Figure 11-9). Thus the supercentrifuge can work for continuous separation of immiscible
liquid phases.

✓ Use: Supercentrifuge is used for separating liquid phases of emulsions in foods and
pharmaceuticals.

Centrifugation