Importance of Size Reduction in Pharmacy: Advantages and Disadvantages

 
 
 
 
 
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Outline of the lecture:
 
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It is the process that reduces large solid unit masses
to smaller unit masses by mechanical means.
 
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:
1.
Increase 
surface area 
which increase the 
solubility
, and
dissolution rate 
of material so enhance its 
bioavailability
.
2.
Improvement of 
extraction rate
.
3.
Improvement and increasing the 
drying rate
.
4.
Improve mixing of materials together so give 
less problems
in uni­formity of weight and contents 
of tablets.
5.
Improve color and/or active ingredient 
dispersion
 in tablet
excipient diluents.
6.
Improve 
flowability
 of materials in tablet machine.
7.
Control particle size distribution of a dry granulation or dry
mix to 
minimize segregation 
while handling and tableting .
 
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1.
A possible 
change in polymorphic 
form of the active
ingredient ren­dering it less or totally inactive or
unstable.
2.
Possible 
degradation of the drug 
as a result of 
heat
build up during milling by 
oxidation or adsorption 
of
unwanted moisture due to the increased surface area.
3.
A decrease in bulk density 
may cause problems in the
flowability of material.
4.
A decrease in particle size may create 
static charge
problems causing the small drug particles to
agglomerate
 therefore effectively 
decreasing surface
area. This may decrease the dissolution rate.
 
Size reduction is a rate process that depends on:
1.
The size of the starting material, the feed.
2.
Type of size reduction machine
3.
The orientation of the material in the crushing
machine.
4.
The time of milling to which these materials are
subjected
 
The principal means of accomplishing size reduction are:
 
1.
Communion
2.
Cutting
3.
Shearing
4.
Compression
5.
Impaction
6.
Attrition, Rubbing
7.
Grinding, Trituration
8.
Chappin
 
A flaw in a unit particle is a discontinuity or imperfection in the structure.
 
Compression at any point along the line below the yield value,
the material will go back and returns to its original shape and
this is called 
elastic deformation.
However compression above the yield value will result in
plastic deformation 
in which the substance break down and not
go back to its original shape after removing stress.
 
Kinds of materials according to the process of size
reduction:
 
1- Brittle
2- Fibrous
3- Hard
 
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The law states that energy required for crushing materials is
proportional to the log­arithm of the ratio between the initial (r
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final diameters (r
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.
                                          Log (r
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:
1.
Producing 
elastic deformation 
of particles before the
occurrence of fractures, which is a waste energy.
2.
Producing 
inelastic deformations 
which lead to size
reduction and this is the wanted energy
3.
Causing 
elastic distortion  
consequently failure of the
equipment
4.
Friction
 between the particles and the machine
5.
Noise, heat and vibration in the plant
.
 
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:
a.
  Friability
b.
  Structure which may be granular, Fibrous
c.
  Hardness
d.
  Stickiness
e.
  Soapiness
f.
  Moisture content
 
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(1)
  The power consumption is less by 20 - 30%.
(2)
   The capacity of the plant is increased.
(3)
    Removal of the product is facilitated and the amount of
        
fines is reduced.
(1)
   Dust formation is eliminated
(2)
   The solids are more easily handled
 
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:
A.
Kind of material.
B.
Initial size of material.
C.
Final product particle size whether we need fine or large particles.
D.
Range of abrasion: some materials are abrasive so we use machine hard
enough which withstand this abrasion effect
.
 
E.
 Moisture content of material whether it is hydrous or anhydrous.
F. Particle size distribution and shape.
G. Structure, strength, friability, stickiness
Hardness of materials are arranged in order of increasing hardness in the
    
Mohr scale
:
   
 
1- Talk 
 
                          4- Fluorspar 
 
7- Quartz
 
         2- Rock salt & gypsum     5- Apotite     
 
8- Topaz
    
 
3-Calcite                           6- Felspar     10- Diamond 
 
9- Carborundum
 
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:
     
The oldest size reduction equipment is Busherstone.
      They are classified according to the products they intended to
produce as 
follows
:
 
1.
Coarse crushers:
 have no applications in pharmacy as blake jaw
crusher, Dodge crusher, Gyratery crusher and Rotary coal breaker
2.
Intermediate crushers 
:
Hammer mills
Cutting mills
Edge and end runner mills.
3.
Fine crushers
:
                  
- Ball mill
                 - Fluid energy mill.
                 - Oscillating granulator.
4.    
Colloidal mills
.
 
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All milling or Comminution equipment Consist of three main or
basic parts: -
1.
Feeding part.
2.
Milling chamber.
3.
Receiver.
 
Some mills are also fitted with
cyclones for classifying the
partcles by size.
 
Outline of the lecture:
 
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Fine
Crushing
 
For Liquids
 
Hammer Mill:
 A, rotating disc; B, shaft; c, hammers; D, breaker plates;
E, screen
 
Intermediate Crushing
 
1- Hammer Mill
 
There are 2 types of Hammer mill
1.
Horizontal - shaft type.   2.    Vertical - shaft type.
 
Advantages of Hammer mill
:
1.
Easy to set up or build
2.
Easy to clean.
3.
Small space requirement.
4.
It has a wide range of the size of feed start.
Disadvantages:
1.
Possibility of clogging of screen
2.
Heat build up during milling and cause degradation of product
so not used for heat labile substances.
3.
Mill and screen wear with abrasive materials
 
2-Cutting Mill:
It is similar to Hammer mill but here, the hammer like knives or blades
Processes
: 
Cutting and shearing.
It is used for fibrous materials, wet and dry materials and for dispersion of
powder. (e.g. liquorices root). It is not used for hard, abrasive materials
3- Edge and End runner mills:
The only advantage is using scraper which can be put on the edge. The feed
is from the top or from side.
Processes
:
 shearing and attrition
 
Fine Crushers
1- Fluid Energy Mill
It is rapid and very efficient method of reducing powders to 
30 
m 
and
less with relatively narrow particle size distribution.
 
Milling takes place immediately because of the high - velocity collisions between
particles suspended within the air steam.
Grinding nozzles (usually 2-6 depending on the size of the mill) may be laced
tangential or opposed to the initial powder flow path to increase the particle
velocity resulting in higher impact energy.
The air from the grinding nozzles transports the powder to a classifier which
removes the smaller particles.
 
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The particle size depends on:
1.
The configuration of the mill
2.
Feed size
3.
Position of the nozzles.
4.
Design of the classifier.
5.
Feed rate.
 
 
 
Ball Mill
 
Types:
 
1.
Batch
2.
Continuous
3.
Continuous closed – circuit milling
 
 
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A.   Batch:
 
It is a cylindrical shell filled to about 1/2 its volume with grinding media with
different sizes.
The shell rotates on its central axis by means of motor- driven rol­lers on which
it rests.
 
B- Continuous:
It is a conical shell with grinding media of different sizes.
Feed enters from the hollow end of the mill and milled material
exits through a grating or small ports of the opposite end.
 
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Another classification of ball mills:
1- Simple ball mill            2- Pebble mill          3-Tube mill
4- Compound ball mill      5- Hardinage mill     6- Rod mill
 
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C. Continuous closed -circuit milling:
It is arranged using the continuous mill with a gas or liquid
classify­ing system.
 
Air and feed enters through the opening at end of the mill.
The large feedstack drops into the milling zone and the smaller
particles become entrained in the air stream flowing through the
mill and exiting through the opposite end to a particle classifier.
The classifier removes the smallest particles while the larger particles
are recycled to the mill inlet for further size reduction.
 
At and above the critical speed, the mill is said to be centrifuging
and grinding of material not occur.
Therefore, milling must be carried out below the critical speed of the
mill at some optimum speed where the balls are carried to the
highest point in the chamber without centrifuging.
 
This speed is dependent on:
1.
Chamber size
2.
Grinding - media size (i.e. Ball size)
3.
Shape, density and size distribution of material.
4.
Amount of material used in the mill.
 
Factors influencing the size of the product in the ball mill:
 
(1) The rate of feed 
 
              (2) Weight of balls
               (3) The diameter of the balls           (4) The slope of the mill
 
(5) Discharge freedom 
 
              (6) The speed.
 
Advantage of the ball mill:
It is used for milling highly abrasive materials.
Disadvantages:
1.
Difficult to clean
2.
Long milling time (i.e. time consuming)
3.
High energy requirements and high cost.
 
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Fine
Crushing
 
For Liquids
 
3- Oscillating Granulator
        
Feed size
 
= 2.0 mm
        
Product size
: 0.3 mm
        
It is used for:
 
the size reduction of wet and dry granulations.
       
Processes:
 Shearing (with some attrition)
 
Principle of operation
:
It consists of an oscillating bar
contacting a woven wire screen. Feed
enters through a hopper above the
oscillator and screen and is forced
through the screen by the oscillating
motion of the bar.
 
Collection of the product may be directly onto trays in the case of
wet granulations or into drums via a sleeve from a specially fitted
collec­tor funnel that minimizes dust during the processing of a
dry granula­tion to collector (dry) trays (wet).
The oscillator speed is constant while the screens can be
interchangea­ble and can produce particle with the desired size
 
Advantages of the oscillating granulator:
1.
Narrow size range.
2.
Minimum amount of fines obtained during size reduction of a dry
granulation.
3.
 Very uniform wet granulation size which promotes uniform drying.
Disadvantages:
1.
Low rate of production
2.
Wear on the screens.
3.
The possibility of product contamination by metal particles chipped/ away
form the screen by the oscillator.
 
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Fine
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For Liquids
 
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Conclusions:
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Size reduction plays a crucial role in pharmacy by enhancing solubility, extraction rate, mixing quality, and more. However, there are also potential drawbacks such as changes in drug stability and flowability issues that need to be considered. Understanding the benefits and limitations of size reduction is essential for optimizing pharmaceutical processes.


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  1. PHT 432) ) Industrial Pharmacy Dr. Fars Alanazi AA91

  2. 2-3 Lectures Lectures Size Reduction

  3. Outline of the lecture: Size Reduction Definition Theory of size reduction Mechanism of size reduction Size reduction equipment 1. Hammer mill, (vertical, horizontal) 2. Cutting mill 3. End and edge runner mill 4. Fluidized energy mill 5. Ball mill and types 6. Oscillating granulator 7. Colloid mill

  4. Definition of size reduction: It is the process that reduces large solid unit masses to smaller unit masses by mechanical means.

  5. Importance of size Reduction in Pharmacy: (Advantages) ?

  6. Importance of size Reduction in Pharmacy: Advantages: 1. Increase surface area which increase the solubility, and dissolution rate of material so enhance its bioavailability. 2. Improvement of extraction rate. 3. Improvement and increasing the drying rate. 4. Improve mixing of materials together so give less problems in uniformity of weight and contents of tablets. 5. Improve color and/or active ingredient dispersion in tablet excipient diluents. 6. Improve flowability of materials in tablet machine. 7. Control particle size distribution of a dry granulation or dry mix to minimize segregation while handling and tableting .

  7. Disadvantages ?

  8. Disadvantages: 1. A possible change in polymorphic form of the active ingredient rendering it less or totally inactive or unstable. 2. Possible degradation of the drug as a result of heat build up during milling by oxidation or adsorption of unwanted moisture due to the increased surface area. 3. A decrease in bulk density may cause problems in the flowability of material. 4. A decrease in particle size may create static charge problems causing the agglomerate therefore effectively decreasing surface area. This may decrease the dissolution rate. small drug particles to

  9. Size reduction is a rate process that depends on: 1. The size of the starting material, the feed. 2. Type of size reduction machine 3. The orientation of the material in the crushing machine. 4. The time of milling to which these materials are subjected

  10. The principal means of accomplishing size reduction are: 1. Communion 2. Cutting 3. Shearing 4. Compression 5. Impaction 6. Attrition, Rubbing 7. Grinding, Trituration 8. Chappin

  11. A flaw in a unit particle is a discontinuity or imperfection in the structure.

  12. Compression at any point along the line below the yield value, the material will go back and returns to its original shape and this is called elastic deformation. However compression above the yield value will result in plastic deformation in which the substance break down and not go back to its original shape after removing stress.

  13. Kinds of materials according to the process of size reduction: 1- Brittle 2- Fibrous 3- Hard

  14. General hardness classification of some pharmaceutical materials: Material Talc Chalk Boric acid Cellulose Aspirin Lactose NH4CI Sucrose Dextrin Sorbitol Kaolin Magnesium oxide Calactate Amobarbital Hardness Soft Soft to brittle Soft Soft but Plastic Moderately hard to brittle Moderately hard to brittle Moderately hard to brittle Moderately hard to brittle Hard to brittle Hard Hard Hard Abrasive Hard Abrasive Very hard Abrasive

  15. Mechanical Engineering Rittinger's law :This law states that the energy required for the crushing process is proportional to the surface sheared, (for fine grinding) Kick's law: The law states that energy required for crushing materials is proportional to the logarithm of the ratio between the initial (r1) and final diameters (r2) of the particles . Log (r1/r2)

  16. Energy may be consumed in so many aspects in the size reduction process as: 1. Producing elastic deformation of particles before the occurrence of fractures, which is a waste energy. 2. Producing inelastic deformations which lead to size reduction and this is the wanted energy 3. Causing elastic distortion consequently failure of the equipment 4. Friction between the particles and the machine 5. Noise, heat and vibration in the plant.

  17. There are factors associated with the nature of the material reduction as: a. Friability b. Structure which may be granular, Fibrous c. Hardness d. Stickiness e. Soapiness f. Moisture content

  18. Grinding can be wet or dry when wet low speed mills are used Advantages of wet grinding (1) The power consumption is less by 20 - 30%. (2) The capacity of the plant is increased. (3) Removal of the product is facilitated and the amount of fines is reduced. (1) Dust formation is eliminated (2) The solids are more easily handled

  19. Selection of size Reduction Equipment depends upon: A.Kind of material. B.Initial size of material. C.Final product particle size whether we need fine or large particles. D.Range of abrasion: some materials are abrasive so we use machine hard enough which withstand this abrasion effect. Hardness of materials are arranged in order of increasing hardness in the Mohr scale: 1- Talk 4- Fluorspar 2- Rock salt & gypsum 5- Apotite 3-Calcite 6- Felspar 7- Quartz 8- Topaz 10- Diamond 9- Carborundum E. Moisture content of material whether it is hydrous or anhydrous. F. Particle size distribution and shape. G. Structure, strength, friability, stickiness

  20. Classification of size Reduction equipment: The oldest size reduction equipment is Busherstone. They are classified according to the products they intended to produce as follows:

  21. Classification of size Reduction equipment 1. Coarse crushers: have no applications in pharmacy as blake jaw crusher, Dodge crusher, Gyraterycrusher and Rotary coal breaker 2. Intermediate crushers : Hammer mills Cutting mills Edge and end runner mills. 3. Fine crushers: - Ball mill - Fluid energy mill. - Oscillating granulator. 4. Colloidal mills.

  22. Classification of size Reduction equipment All milling or Comminution equipment Consist of three main or basic parts: - 1. Feeding part. 2. Milling chamber. 3. Receiver. Some mills are also fitted with cyclones for classifying the partcles bysize.

  23. Outline of the lecture: Size Reduction Definition Theory and mechanisms of size reduction Mechanism of size reduction Size reduction equipment 1. Hammer mill, (vertical, horizontal) 2. Cutting mill 3. End and edge runner mill 4. Fluidized energy mill 5. Ball mill and types 6. Oscillating granulator 7. Colloid mill

  24. 1. Hammer mill, (vertical, horizontal) 2. Cutting mill 3. End and edge runner mill 4. Fluidized energy mill 5. Ball mill and types 6. Oscillating granulator 7. Colloid mill Intermediate Crushing Fine Crushing For Liquids

  25. Intermediate Crushing 1- Hammer Mill Hammer Mill: A, rotating disc; B, shaft; c, hammers; D, breaker plates; E, screen

  26. There are 2 types of Hammer mill 1. Horizontal - shaft type. 2. Vertical - shaft type.

  27. Types of screen bars for hammer mills

  28. Advantages of Hammer mill: 1. Easy to set up or build 2. Easy to clean. 3. Small space requirement. 4. It has a wide range of the size of feed start. Disadvantages: 1. Possibility of clogging of screen 2. Heat build up during milling and cause degradation of product so not used for heat labile substances. 3. Mill and screen wear with abrasive materials

  29. 2-Cutting Mill: It is similar to Hammer mill but here, the hammer like knives or blades Processes: Cutting and shearing. It is used for fibrous materials, wet and dry materials and for dispersion of powder. (e.g. liquorices root). It is not used for hard, abrasive materials 3- Edge and End runner mills: The only advantage is using scraper which can be put on the edge. The feed is from the top or from side. Processes: shearing and attrition

  30. Fine Crushers 1- Fluid Energy Mill It is rapid and very efficient method of reducing powders to 30 m and less with relatively narrow particle size distribution. Processes: Attrition and impaction. Principle of operation: A high-velocity air stream introduces the powder to the milling chamber by a venturi tube (a high - velocity air stream passing an opening containing the powder produces a vacuum in the opening and draws the powder into the air stream)

  31. Milling takes place immediately because of the high - velocity collisions between particles suspended within the air steam. Grinding nozzles (usually 2-6 depending on the size of the mill) may be laced tangential or opposed to the initial powder flow path to increase the particle velocity resulting in higher impact energy. The air from the grinding nozzles transports the powder to a classifier which removes the smaller particles.

  32. Schematic of fluid energy mill and particle collection system

  33. The particle size depends on: 1. The configuration of the mill 2. Feed size 3. Position of the nozzles. 4. Design of the classifier. 5. Feed rate. If the feed rate is high larger particle size could be obtained If the feed rate is slow smaller particle size could be obtained

  34. 1. Heat -labile sbubstances can be milled with little danger of thermal degradation. This is because of the cooling effect of the air and rapid heat exchange between particles and air. 2. It produces very small and uniform distributed particles. 3. Inert gases can be used instead of air to minimize or Advantages: eliminate the oxidation of susceptible compounds which may occur with compressed air. Ultra-fine grinding Materials: Moderately hard 20 - 200 mesh gives 30-5 m or less. Materials not recommended for mill soft, tacky, fibrous Uses:

  35. Ball Mill Types: 1. Batch 2. Continuous 3. Continuous closed circuit milling

  36. http://upload.wikimedia.org/wikipedia/commons/4/4f/High-energy_ball_milling.gifhttp://upload.wikimedia.org/wikipedia/commons/4/4f/High-energy_ball_milling.gif http://upload.wikimedia.org/wikipedia/commons/c/c2/Ball_mill.gif http://upload.wikimedia.org/wikipedia/commons/thumb/1/1d/8000M_Mixer_Mill_%28open%29_incl_accessories.jpg/220px-8000M_Mixer_Mill_%28open%29_incl_accessories.jpg

  37. Ball Mill A. Batch: It is a cylindrical shell filled to about 1/2 its volume with grinding media with different sizes. The shell rotates on its central axis by means of motor- driven rollers on which it rests.

  38. B- Continuous: It is a conical shell with grinding media of different sizes. Feed enters from the hollow end of the mill and milled material exits through a grating or small ports of the opposite end.

  39. Harding Mill Conical mill chamber Grating Feedstock in Milled product out Grinding media

  40. Another classification of ball mills: 1- Simple ball mill 2- Pebble mill 3-Tube mill 4- Compound ball mill 5- Hardinage mill 6- Rod mill Discharge end Hardinage mill Feed end

  41. C. Continuous closed -circuit milling: It is arranged using the continuous mill with a gas or liquid classifying system.

  42. Air and feed enters through the opening at end of the mill. The large feedstack drops into the milling zone and the smaller particles become entrained in the air stream flowing through the mill and exiting through the opposite end to a particle classifier. The classifier removes the smallest particles while the larger particles are recycled to the mill inlet for further size reduction.

  43. At and above the critical speed, the mill is said to be centrifuging and grinding of material not occur. Therefore, milling must be carried out below the critical speed of the mill at some optimum speed where the balls are carried to the highest point in the chamber without centrifuging.

  44. This speed is dependent on: 1. Chamber size 2. Grinding - media size (i.e. Ball size) 3. Shape, density and size distribution of material. 4. Amount of material used in the mill. Factors influencing the size of the product in the ball mill: (1) The rate of feed (2) Weight of balls (3) The diameter of the balls (4) The slope of the mill (5) Discharge freedom (6) The speed.

  45. Advantage of the ball mill: It is used for milling highly abrasive materials. Disadvantages: 1. Difficult to clean 2. Long milling time (i.e. time consuming) 3. High energy requirements and high cost.

  46. 1. Hammer mill, (vertical, horizontal) 2. Cutting mill 3. End and edge runner mill 4. Fluidized energy mill 5. Ball mill and types 6. Oscillating granulator 7. Colloid mill Intermediate Crushing Fine Crushing For Liquids

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