1. DEPARTMENT OF PHARMACEUTICS .
MILLING AND MIXING ,
DEPARTMENT OF PHARMACEUTICS .

2. CONTENTS :
MILLING :
Introduction to size reduction.
Objectives of size reduction.
Modes in size reduction.
Classification of pharmaceutical miller.
Factors effecting selection of a mill.
MIXING :
Introduction
Types of mixtures
Mixing of solids
Factors effecting mixing.
Powder mixing equipment.
Mixing of miscible liquids and suspensions.
Mixing of immiscible liquids.
Mixers of semisolids

3. MILLING :
INTRODUCTION:
Size reduction is a process of reducing large solid unit masses into small unit masses, coarse particles or fine particles.
Size reduction process also termed as comminution or diminution or pulverisation.
Size reduction may be achieved by TWO methods
Precipitation process
Mechanical process

4. Precipitation process :
Substances is dissolved in an appropriate solvent. Subsequently, it is finely precipitated by the addition of another solvent.
Which is miscible with the first, but in the later substance is insoluble.
This method is suitable for the production of raw materials and bulk drugs.
Mechanical process:
The substances is subject to mechanical forces using grinding equipment.
E.g.: ball mill, roller mill, colloid mill……. Etc
Dry grinding or milling is used in the production of tablets, capsules.
Wet grinding is used in the preparation of suspensions, emulsions and ointments.

5. OBJECTIVE OF SIZE REDUCTION :
It improves appearance.
It increases surface area.
It facilitate absorption and bioavailability.
It improves the stability.
It facilitate extraction.
It facilitate mixing.
In aerosol and inhalation preparation.
Parental suspension.
It facilitate drying.
Ophthalmic suspension.
Increase in viscosity.
ADVANTAGES:
Content uniformity
Uniform flow
Effective drying
Improved physical stability
Improved dissolution rate
Improved rate of absorption
DISADVANTAGES:
Drug degradation
Poor mixing
Contamination

6. Modes of size reduction:
Cutting: The material is cut by means of a sharp blades
Eg : cutter mill
Compression:
In this mode material is crushed between roller by the application of pressure Eg : roller mill
Impact:
This involve the operation of hammer/bars at high speeds.
When a lump of material strikes the rotating hammers, the material splits apart Eg : fluid energy mill
Attrition: breaking down by the rubbing action between two surfaces Eg : fluid energy mill

7. CLASSIFICATON OF SIZE REDUCTION EQUIPMENT:
Crushers: ex: edge runner mill, end runner mill.
B. Grinders :
1.impact mill: ex: hammer mill
2. rolling compression: ex: roller mill
3. attrition mill: ex: attrition mill
4. tumbling mill: ex: ball mill
Ultrafine grinder: ex: fluid energy mill
Cutting machine : ex: cutter mill
The milling or grinding equipment consist of three basic components.
1. Hopper
2. Rotor and stator
3. A discharge chute.

8. ROTARY CUTTER MILL :
Principle:
cutting
Construction:
contains two types of knives.
The horizontally mounted rotor disc consists of 2 to 12 knives spaced uniformly.
The casing also has several stationary knives
Working: the rotor disc is allowed to rotate at speeds from 200 to 900 rpm
The particle size and shapes are determined by the rotor size , gap between the rotating & stationary knives and opening of the sieve
Uses : size reduction of the tough and fibrous material.

9. Roller mill :
Principle: stress&attrition
Construction: it consists of two cylindrical rollers made of stone or metal
Rollers are capable of rotating on their longitudinal axes.
One roller is driven directly using a motor, while second one runs freely.
The gap between the rollers can be controlled to obtain the desired particle size.
Uses: used for crushing and cracking of seeds before extraction of fixed oils.

10. Hammer mill :
Principle: Impact
Construction: hammers are fitted horizontally or vertically made up of hardened steel
Hammers blades can be flat edges or sharp edges or both on each side
Working: Rotates at 8000 to 15000rpm
variants:
Fitz patrick communicating mill.
Stokes tornado mill

11. Uses: Obtained particle size is 10 to 400mm.
Used to mill dry materials,ointments,slurries,wet filter press cakes.
Advantages:
It is versatile, occupies small space.
Operation in close system,dust can be reduced
Easy to setup and scale up.
Disadvantages: Screens may get clogged.
More heat is generated.
Not to mill sticky, fibrous, hard materials
Ball mill :
Principle: In the ball mill, Impact or attrition or both are responsible for the size reduction.
Construction: consists of horizontal cylinder containing balls that occupy 30 to 50% of the mill volume.
Working: The drug is placed upto 60% of volume.

12. Low speed
Correct speed
High speed

13. Uses: Size of 5 to 100 mm or less are obtained.
Ophthalmic and parenteral products can be produced.
Advantages: Produce very fine powders
useful for both dry and wet grinding.
Toxic substances can be milled.
Sterile products can be milled.
Disadvantages:
Noisy
Slow process
variants: hardening mill
Continuous ball mill
Vibrating ball mill.

14. Fluid energy mill
Principle: Impact and attrition
Construction: elipitical tube of 2 mts height and 20 to 200 mm diameter.
2 to 6 grinding nozzles are present.
Compressed air of 600kilopascals to 1.0 megapascals is normally used.

15. Uses: To reduce most of the antibiotics, vitamins.
Advantages: Heat is not produced.
No contamination.
Reducing powders to 30 mm or less.
Disadvantages : Expensive
Not used for milling of soft tacky and fibrous materials.
Colloid mill :
Principle: shearing
construction:
It consists of rotor & stator
The clearance between the rotor & stator can be adjusted from 0.05 to 0.75 mm.
Working:
Solids are mixed with liquid vehicle before introduced into the colloid mill.
The rotor rotates at 3000 – rpm .

16. Uses:
Preparing colloidal dispersions, Suspensions, emulsions and Ointments.
Particle size as small as 3 µm can be obtained
Advantages:
High capacity with minimal space requirements.
Rapid handling and easy cleaning
It can be used in the production of sterile products.
Disadvantages :
Its not use for dry milling
Heat is generated during milling

17. Edge runner mill :
principle:
crushing & shearing force is also involved during the movement of stones.
Construction:
It consist of two heavy rollers . The rollers moves on bed. which is made of stone or iron
Each roller has a central shaft and revolve on its axis.
The rollers mounted on a horizontal shaft & move around the bed.

18. Working:
The stones revolve on its own axis, and at the same time travel round the shallow stone bed.
Size reduction achieved by shearing as well as crushing.
Its is a batch process
Uses : Grinding of tough materials and plant based products.
Disadvantages: occupies more space.
Contamination is more.
Time consuming process.

19. End runner mill :
Principle: Crushing due to weight of pestle and shearing also involves.
Construction: Consists of mechanical mortar and pestle which can rotate at high speed.
Steel mortar, which is fixed to a flanged plate is present.
Pestle is dumb-bell shaped.
Pestle can be raised from the mortar to facilitate emptying and cleaning.
Working: mortar revolves at high speed the revolving mortar causes the pestle to revolve.
Uses: suitable for fine grinding
Disadvantages: not suitable for drugs which are unbroken or slightly broken condition.

20. MULTI MILL :
Multi mill machines are widely used for wet and dry granulation, pulverization etc.
These machines find application in pharmaceutical, chemical, bulk drug, cosmetic, dyestuffs and food processing industries.
The unit consists of vibro sifter, tablet coating pan, spray coating machine and dust extractor

21. It operates on the principle of variable force swing beaters having both knife and impact edges rotating within a selected screen to get the required size reduction.
Material fed in the hopper, goes down to the processing chamber where it moves to the periphery and passes through the screen radially and tangentially.
Finally the processed material gets collected in the container kept below the processing chamber .
Output and quality of the final product depends on three main factors : (1) Shape of beaters (knife/impact edges), (2) Speed and (3) Screen. d based on the specific requirements of the clients.

22. Name of the mill
principle
construction
Working
Uses
Advantages
Disadvantages
Rotary Cutter mill
cutting
Consists various types of knives.
rpm
Size reduced fine 80#-100#
Not suitable for friable material
Roller mill
Stress & Attrition
Two rollers are rotates longitudinally
Crushing b/w rollers
Crushing of seeds for extraction
Abrasive materials
Ball mill
Both impact & attrition
Hollow cylinder& balls occupy 30%-50% space
drug is occupy upto 60% of volume.
Speed of rotation is imp.
Grind brittle drugs to fine powder
Toxic & sterile substances can be milled.
Noisy
Hammer mill
Impact
Hammers present either sharp or flat edges
Rotates at 8000 to 15000rpm
grinding dry materials, wet filter cakes, ointments,
Operation in close system.
Easy to setup and scale up.
Screens may get clogged

23. Name of mill
Principle
Construction
Working
Uses
Advantages
disadvantages
Fluid energy mill
Impact & attrition
2 to 6 grinding nozzles
air 600 kilopascals to 1.0 Mpa.
Due to high degree of turbulence, impact & attrition occur b/w particles
Moderately hard & friable materials
reduce particle size 1 – 20µ
Softy & silky material are not suitable
Colloid mill
Shearing
rotor & stator discs.
3,000-20,000 r.p.m
0.001 inch to size adjustment
Preparation of ointment, cream, gels
Rapid handling and easy cleaning.
Can’t use for thermoliable& emulsion type materials
Edge runner mill
Crushing & shearing
rollers made up of with stone
Rollers have shaft & revolve its own axis
Grinding of plant based products.
Less attention during operation
Sticky materials are not used
End runner mill
Crushing & shearing.
Consists of mechanical mortar and pestle
mortar revolves at high speed
suitable for fine grinding
Drugs which r unbroken

24. SELECTION OF MILL:
Factors related to the nature of raw materials
Hard materials
Fibrous material
Friable material
Elastics material
Hygroscopic material
Melting point
Particle size of the material
moisture content.
Thermolability.
Factors related to nature of finished product:
particle size, ease of sterilization , contamination of milled product.
Factors related to safety:
explosivity, irritability, toxicity.
Factors related to economy:
cost, power consumption, space occupied and labor cost.

25. MIXING
INTRODUCTION:
“mixing is an unit operation, that tends to result in a randomization of
dissimilar particles with in a system”
If each unit of the components is lies in contact with a unit of other components that was called perfect mix.
In practice the best type of mix is randomized mix. In randomized mix the ratios of the components in the entire mixer is same.
In practice the best type of mix is randomized mix. In randomized mix the ratios of the components in the entire mixer is same.
PERFECT MIX

26. TYPES OF MIXTURES: Dank wert classified mixtures in to three types
1.Positive Mixtures
2.Negative Mixtures
3. Neutral Mixtures
POSITIVE MIXTURES :
Positive mixtures formed from miscible liquids and gases which mix spontaneously
Ex: miscible liquids.
NEGATIVE MIXTURES :
Negative mixtures are formed from the components , they will tend to separate out. Ex: emulsions , creams suspensions
Negative mixtures are formed from the components,they will tend to separate out.
NEUTRAL MIXTURES:
In neutral mixtures the components have no tendency to mix spontaneously or segregate spontaneously once work has been input to mix them.
Ex: pastes and ointments.

27. POWDER MIXING EQUIPMENT:
MIXING OF SOLIDS:
solid – solid mixing can be obtained by three main mechanisms
1. Convection mixing
2. Shear mixing
3. Diffusion mixing
POWDER MIXING EQUIPMENT:
TUMBLING MIXERS:
Tumbling mixers are commonly used for the mixing of granules and free flowing powders.
Ex: double – cone mixer, twin – shell mixer, cube mixer
These mixing containers are generally mounted so they can rotated about an axis. When operated at correct speed tumbling action will achieved.
Shear mixing will occur when velocity gradient is produced.
The addition of baffles or rotating bars will also cause convective mixing.
A common use of tumbling mixers is blending of lubricants, glidants and external disintegrants with granules prior to tableting.
tumbling mixers are commonly used for the mixing of granules and free flowing powders

28. Octagonal blender
Octagonal blender
V – cone tumbling mixer

29. FLUIDIZED – BED MIXERS
Fluidized – bed mixers are used to mix powders prior to granulation. it is very efficient mixing process.
In this the powder particles are fluidized in the stream of air, granulation fluid is sprayed from a nozzle on to the bed of powder.
The fluid causes powder to adhere when the droplets and powders collide.
Sufficient liquid is sprayed to produce granules of required size
Then the wet granules dried in the heated air stream.
fluidized – bed mixers are used to mix powders prior to grnulation

30. AGITATOR MIXERS:
This type of mixtures depends on motion of a blade or a paddle through the product.
The main mechanisms of mixing is convection and shear.
Ex: Ribbon mixer, planetary mixer
RIBBON MIXER:
It consist of non moveable horizontal cylindrical trough and helical blade which is mounted on a drive shaft through the long axis of the trough.
The main mechanism of mixing is shear.
Ribbon mixers are used for mixing of wet solid mass, liquid solid mixing
It consist of non moveable horizontal cylindrical trough and helical blade which is mounted on shaft through the long axis of the trough

31. The planetary mixer consist of rotating blade, and stationary bowl.
The mechanism of mixing is shearing.
The rotating blade rotates in its own axis and around the central axis so, there is no dead spots in the mixing and high shear is applied for mixing.
Planetary mixer used for dry blending, wet granulation and ointments.

32. FACTORS EFFECTING MIXING:
Particle characteristics influence the mixing process
1. particle surface.
2. density of particle.
3. particle size.
4.particle shape.
5.proportion of materials.
EVALUATION OF THE DEGREE OF MIXING
The degree of mixing is evaluated by comparing the content standard deviation of sample under investigation ( SACT ) with that samples from a fully random mix (SR ).
Mixing index (M) = SR SR
SACT

33. MIXING OF MISCIBLE LIQUIDS AND SUSPENSIONS:
MIXING OF THE LIQUIDS :
Liquids are mixed by three main mechanisms
1. bulk transport.
2. turbulent mixing.
3. molecular diffusion.
MIXING OF MISCIBLE LIQUIDS AND SUSPENSIONS:
Agitated vessels are commonly used for mixing of miscible liquids and suspensions. It contains impellers and baffles.
These vessels are cylindrical in shape and having conical or contoured base .
IMPELLERS :
Impellers supply energy for the mixing it cause flow of fluid in to three directions
Impellers supply energy for the mixing. It cause flow of fluid in to three directions. 1. Radial, 2. Axial , 3. Tangential .

34. Baffled tank: no vertex
Un baffled tank: vertex formation
Motor
Shaft
Baffle
Impeller

35. 1 . Radial flow – perpendicular to the impeller shaft
2 . Axial flow – parallel to the impeller shaft
3 . Tangential flow – tangential to circle of rotating shaft. .
Based on the shape of the blades and flow pattern produced by them , these impellers are classified as
Axial flow
Radial flow

36. Based on the shape of the blades and flow pattern produced by them ,
these impellers are classified as
1. propellers.
2. turbines.
3. paddles .
PROPELLERS :
propellers produce axial flow.
Used for mixing of low viscous solutions.
Operated at 400 – 1750 RPM.
High speeds are used for low viscous solutions.
Used for mixing of elixirs and disinfectant solutions

37. Turbines consist of number of blades attached on circular disk
Turbine mixers used for more viscous fluids. Operated at 50 – 200 RPM.
Different shapes of blades like straight, curved , pitched etc are used in turbines.
Straight and curved blades produce radial and tangential flow, pitched blades produce axial flow,
Turbine mixers are used for mixing of syrups, slurries.
PADDLES:
Paddles consist of a central hub to which 2 long flat blades are attached.
It produce radial or tangential flow.
Used for the preparation of suspensions.
Flat blade turbine
Curved vane turbine
Disk turbine

38. This is typically achieved with an external recirculation pump.
JET MIXER :
In jet mixers a stream of liquid injected at high velocity in the bulk of another miscible liquid.
This is typically achieved with an external recirculation pump.
Jet mixing is suitable for the low viscous solutions.
In jet mixers a stream of liquid injected at high velocity in the bulk of another liquid
Recirculation pump

39. MIXING OF IMMISCIBLE LIQUIDS:
Mixing of immiscible liquids is carried out in the preparation of emulsions.
ex: Silverson mixer, colloidal mill
SILVERSON EMULSIFIER:
Silverson emulsifier consist of long supporting columns connected to a motor which give support to head.
Central portion consist of shaft connected to motor and head.
Head carries turbine blades. Surrounded by a mesh, which is enclosed by cover having openings.
When head is placed in mixing vessel containing immiscible liquids. When motor started pressure difference is created, liquids are sucked into the head and subjected to intense mixing action.
Silverson emulsifier consist of long supporting culumns connected to a motor and other end connected to head

40. Silverson homogenizer
Colloidal mill
Silverson homogenizer

41. It is used in the preparation of emulsions, suspensions and ointments.
COLLOID MILL:
Colloid mill based on the principle of attrition between the stator and rotor.
It is used in the preparation of emulsions, suspensions and ointments.
The rotor is revolving ay 3000 – rpm.
The feed is forced by the rotor through narrow gap between rotor and stator and intense mixing , size reduction takes place.
Colloid mill is suitable for high viscous solutions(30000c.p)
Colloid mill based on the principle of attrition between the stator and rotor

42. Ex: planetary mixer, sigma blade mixer.
MIXING OF SEMI SOLIDS:
Mixing of semi solids is difficult compare to the liquids and powders. These materials will not flow easily, dead spots will remain there.
So, the mixers with narrow clearances and high degree of sear mixing produce should select.
Ex: planetary mixer, sigma blade mixer.
SIGMA BLADE MIXER:
The mechanism of mixing is shearing.
It consist of a stationary bowl and two sigma shaped blades fitted horizontally
in bowl.
These blades are connected to fixed speed drive.
The material is sheared between the blades and walls of bowl.
Sigma blade mixer is used for mixing of semisolids, wet granulation process.
SIGMA BLADE MIXER

43. REFERENCES:
M.E AULTON; PHARMACEUTICS, SECOND EDITION; Pg no:
LEON LACHMAN;HERBERT A. LIEBERMAN ; THE THEORY AND PRACTICE OF
INDUSTRIAL PHARMACY.;P
A.R PARADKAR; ITRODUCTION TO PHARMACEUTICAL ENGINEERING . Pg no.141
C.V.S. SUBRAHMANYAM et al; pharmaceutical engineering. Pg no. 199

44. ThankYou
JAI HIND