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1. By: Chernet T. (B.Pharm., M.Sc. in
Pharmaceutics)
Bahir Dar University, CMHS, Department of
Pharmacy
1
Unit operations in Pharmaceutical
Technology
Love Each Other

2. Outline
2
 INTRODUCTION
 Pharmaceutical technology
 Industrial pharmacy
 Unit operations
 Size reduction
 Size separation
 Mixing
 Drying
 Filtration and clarification

3. Pharmaceutical technology
3
 Pharmaceutical Technology is an applied science for the development, manufacture
and testing of dosage forms
 It is application of scientific knowledge or technology to pharmacy and
the pharmaceutical industry
 It covers
 Pre-formulation, formulation, manufacturing and packaging
Equipment and instruments used for production, QC , QA & cGMP
 Unit operations in manufacturing of drugs
 The role of genetic engineering in the dev’t of pharmaceutical products
 Biopharmaceuticals

4. Pharmaceutical technology
4
 Industrial pharmacy is one discipline in the pharmaceutical
technology concerned with:
The theoretical and practical aspects of pertinent unit
operations
 Milling, mixing, drying, filtration, centrifugation, crystallization
Formulation, manufacturing and packaging of
 d/nt dosage forms
Equipment and instruments used for Production, quality control,
overall quality assurance and cGMP

5. 5
Unit operations

6. Objectives
6
 At the end of this sub-topic, the student will be able to:
 Define size reduction
 Discuss the pharmaceutical applications of particle size
reduction
 Describe the mechanisms of particle size reduction
 The equipments commonly used for particle size reduction
 Define size separation
 Knows the pharmaceutical application of size separation
 Understand the different techniques of size separation

7. Pharmaceutical processing
7
 Drugs are not used “as they are”
 They need to be processed
I. Isolation of the active drug
II. Conversion of the drug into medicine

8. 8
Pharmaceutical processing..

9. Breakdown of process
9
 The number of individual processes in pharmaceutical factory
is great and the process seems complicated
 Each one can be broken down into a series of steps, called
operations.
 Pharmaceutical manufacturing processes can be divided into
a number of process called unit operations

10. Unit operations
10
 Unit operations in pharmaceutical technology refers to
 The individual operations/processes that make up the whole process of drug
manufacturing.
 A process may have many unit operations to obtain the desired product.
 The common unit operations or processes involved are:
Size reduction
Size separation
Mixing
Drying
 Filtration
 Centrifugation
 Crystallization

11. Particle Size Reduction
11
 Materials are rarely found in the required size range.
 It is often necessary either to decrease or to increase the particle size.
 In simple term:
So, size reduction means decreasing the size of an object or material

12. Size reduction
12
Definition:
 It is a unit operation in which materials are reduced to a finer/coarser
particles before they are formulated into a suitable dosage form.
 The operation is carried out to obtain the desired size with the help of d/nt
equipment's.
 It is also referred as
o Comminution, grinding, milling, pulverization or crushing

13. Particle Size Reduction...
13
Objectives of Size Reduction
 Increase surface area
 Increase the area of contact b/n the solids and the dissolving fluid
 This will help in rapid dissolution
 Facilitate Absorption & Bioavailability
 An increased dissolution rate, increased bioavailability and Increase
therapeutic efficiency.
 The extraction of crude drugs is facilitated with an increase in surface area b/c
 solvent can easily penetrate into the tissues resulting in quick extraction of
their active constituents

14. Particle Size Reduction...
14
 Improve mixing efficiency
 The mixing of several solid ingredients is easier and more uniform if the
ingredients are reduced to narrow size range.
 Content uniformity
 Improve the quality of certain dosage forms
 The physical appearance of ointments, pastes and creams can be improved by
reducing its particle size.
 Smooth texture and elegant appearance
 All the ophthalmic preparations must be free from gritty particles to avoid
irritation of the eye

15. Particle Size Reduction...
15
 Facilitate drying rate
 Drying of wet masses can be facilitated by milling.
 Milling → ↑surface area → ↑Drying.
 Reduce the distance the moisture must travel within the particle to reach the surface of
the solid
 Improve Stability
 Size reduction with subsequent drying increases stability of moisture sensitive materials
 Emulsion – Reduced Size of oil droplets results in reduction in rate of creaming
 Suspension – Reduced Size of particles results in a decrease in rate of sedimentation

16. 16
Disadvantages:
 A possible change in polymorphic form of the active ingredient
 Possible degradation of the drug as a result of heat buildup during
milling.
 Adsorption of unwanted moisture due to the increased surface area.
 May cause problems in the flowability
 A decrease in particle size may create static charge problems causing
agglomeration, decreasing surface area.

17. Particle Size Reduction...
17
Mechanisms of size reduction
 Cutting (Slicing)
 Compression
 Impact
 Attrition
 Size reduction methods
 If you are given a chalk, an incense, a stone and ordered to reduce
their size, how can you do that?

18. 18
Method Mechanism Equipments Use
Cutting
Here the material is cut into pieces by means of a
sharp blade or blades.
Cutter
mill
fibrous crude
drugs
Compression
(pressure)
The material is crushed by application of pressure.
Particles disintegrate by two rigid forces.
Compressi
on mill
Soft
materials
Impact The material is more or less stationary and is hit by
an object moving at high speed
 A moving particle strikes a stationary surface.
Hammer
mill
Almost all
drugs
Attrition The material is subjected to pressure as in
compression, but the surfaces are moving relative
to each other, breakdown of materials result from
rubbing action of two surfaces
Roller
mills
Soft and
fibrous
materials
Attrition and
impact
Combined impact and attrition methods
Ball, Fluid
energy, Pin
mills

19. 19

20. Methods and equipments
20
 All milling equipments consist of three basic parts:
1. Feeding part (feed chute): to deliver the material
2. Milling chamber: where size reduction takes place
3. Receiver: to discharge size reduced product
 Some are also fitted with
dust collector
Sieves/screens for classifying the particles by size

21. Cutter mill
21
 Consists of a series of knives attached to rotor which
act against a series of stationary knives attached to the
mill covering.
 Feed enters through the top hopper.
 The rotor rotates and both stationary and rotating
knives cut the material into pieces.
 The lower part consists of a screen, so that material is
retained in the mill until sufficient degree of size
reduction has been achieved.

22. Cutter mill
22
 Advantages
 Easy to clean, operate and maintenance cost is less
 Less wear and tear
 Good for coarse grinding.
 Wide range of materials (soft-fibrous-tough).
 Roots ,peels or barks prior to extraction
 Sieve being detachable – different sizes can be used
as per need.
 Disadvantages
 Not suitable for fine grinding.
 Very hard material cannot be
grinded.
 Sticky materials cannot be used.

23. Hammer mill
 Principle: Impact
 Upper part – Feed hopper.
 Lower part – Screen of desired size, through
which materials can escape, when sufficiently
size reduced.
 Screen is replaceable as per size required.
 It essentially contains rotating central shaft to
which hammers are attached.
 The hammers swing out to a radial position
when the shaft is rotated.

24. Hammer mill...
24
 Advantages
 It is rapid in action, and is capable of grinding many different types of materials
(Versatility)
 The product size can be controlled by variation of rotor speed hammer type and size and
shape of mesh.
 Disadvantages
 High speed of operation generates heat that may affect thermo-labile materials or drugs
containing gum, fat, resin or other sticky material
 Not useful for abrasive material

25. Fluid energy mill
25
Working principle: material is reduced in size
by attrition and impact
 A fluid usually air, is injected at very high pressure.
 The feed stock is suspended within a high velocity stream
of air.
 The high kinetic energy of the air causes the particles to
impact-with each other with sufficient momentum for
fracture to occur.

26. Fluid energy mill...
26
 The high velocity of the air gives rise to zones of turbulence.
 Turbulence ensures that the level of particle-particle collisions is high
enough to produce substantial size reduction by impact and some attrition.
 There is an internal classifier, by which finer & lighter particles are
discharged and heavier particles are retained until reduction to small size.
 The finer particles are dragged by air suck leaving the mill, while larger, heavy
particles are carried downward to the grinding chamber

27. Fluid energy mill...
27
 Advantages
 The particle size of the product is smaller than that produced by any other method of
size reduction.
 Gases at the nozzles lead to cooling, counteracting the usual frictional heat that can
affect heat-sensitive (thermo-labile) materials.
 Since the size reduction is by inter-particulate attrition there is little or no abrasion of
the mill and no contamination of the product.
 Disadvantage
 High cost, High energy consumption
 Limited production capacity , premilling is required

28. 28
Particle-size separation

29. Particle-size separation
29
 Size reduction results in particles of somewhat varying sizes.
 To control the particle size distribution, the size-reduced material must be sifted to
get fractions of narrow size ranges.
 Particle size separation: is a unit operation that involves the
separation of mixture of various size of particles into two or more
portions with the help of d/nt techniques

30. Size Separation
30
 Standards for powders for pharmaceutical purposes are laid down
principally in the Indian Pharmacopoeia.
 it states that the degree of coarseness or fineness of a powder is
differentiated by the size of the mesh of the sieve through which it passes.
 The IP specifies five grades of powder and the number of the sieve
through which all the particles must pass.
Grade of powder Sieve through w/h all particles must pass
Coarse 10
Moderately coarse 22
Moderately fine 44
Fine 85
Very Fine 120

31. Particle-size separation
31
 Methods of particle size separtaion.
I. Size separation by sieving
 Agitation
 Brush the sieve
II. Size separation by fluid classification
 Sedimentation methods
 Elutriation methods

32. Size separation by sieving
32
 Size separation of powder is done by passing the powdered material through a set of
sieves.
 Sieves are arranged in descending order i.e. sieve of larger size is at the top and the
smallest one at the bottom.The bottom sieve is attached to the receiving pan.
 The number of the sieve indicates the number of meshes included in a length of 25.4
mm (1inch) in each direction parallel to the wires
 A No. 5 sieve has 5 meshes per inch in each direction

33. Size separation by sieving
33
 Agitation methods
 Size separation is achieved by electrically or mechanically induced oscillation
or vibration of the sieve meshes
Oscillation:The sieve is mounted on a frame that oscillates back and forth.
 It is a simple method but the material may roll on the surface of the sieve
Vibration : The sieve is vibrated at high speed by means of an electric
device.
 The rapid vibration helps small enough particles to pass through it.
 less likely to clog due to rapid vibration

34. Size separation by sieving
34 Size separation by vibration

35. size separation by sieving
35
 Brushing methods
 A brush is used to move
 particles on the surface of the sieve and
 to keep the meshes clear and prevents openings blockage.
 Sieving is the most widely used method for particle size analysis
• In-expensive , simple , rapid, and Llittle variation between operators

36. size separation by fluid classification
36
 A methods of particle size separation based on sedimentation or on
elutriation
 Sedimentation methods
 Utilizes the differences in settling velocities of particles with different
size and density

37. Continued…..
37
 The division of particles into size fractions depends on the time of sedimentation.
 Size fractions can be collected after predetermined times.
 Disadvantages of this method
 It does not give a clean split of particle sizes
 Because some small particles will be near the bottom of the tank at the beginning of
the process and so will be removed with the coarse particles.

38. Continued…….
38
 Elutriation methods
o Elutriation is a process for separating particles based on their size and density, using a
stream of gas flowing in a direction opposite to the direction of
sedimentation.
o If the upward velocity of the fluid is less than the settling velocity of the
particle, sedimentation occurs and the particle moves downwards against
the flow of fluid.

39. Particle-size separation
39
 Conversely, if the settling velocity of the particle is less than the upward
fluid velocity, the particle moves upwards with the fluid flow.
 Therefore, in the case of elutriation, particles are divided into different
size fractions depending on the velocity of the fluid.

40. Particle-size separation
40
 Separation of powders into several size fractions can be effected by using a
number of elutriators connected in series.
 The suspension is fed into the bottom of the narrowest column, overflowing
from the top into the bottom of the next widest column and so on.
 As the column diameter increases; the fluid velocity decreases and therefore
particles of decreasing size will be separated.

41. Particle-size separation
41
The smallest diameter

42. 42