PM3125: Lectures 18 to 21

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PM3125 Lectures 18 to 21

• Content of Lecture 18
• Compression Compaction in Tablets Formation

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Principle of tablet production
Active substance synthesis
Blending and Granulation
Compression
Coating
Package
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Compressed tablets

• Advantages and disadvantages of compressed
  tablets
• Types of tablets
• Tablet compression machine
• Tableting methods

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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Advantages

• Production aspect
• Large scale production at lowest cost
• Easiest and cheapest to package and ship
• High stability
• User aspect (doctor, pharmacist, patient)
• Easy to handling
• Lightest and most compact
• Greatest dose precision least content
  variability
• Coating can mark unpleasant tastes improve
  acceptability

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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Disadvantages

• Some drugs resist compression into dense compacts
• Drugs with poor wetting, slow dissolution,
  intermediate to large dosages may be difficult or
  impossible to formulate and manufacture as a
  tablet that provide adequate or full drug
  bioavailability
• Bitter taste drugs, drugs with an objectionable
  odor, or sensitive to oxygen or moisture may
  require encapsulation or entrapment prior to
  compression or the tablets may require coating

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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Types of tablets Production process

• Compressed tablets
• Multiple compressed tablets
• Tablet within a tablets core and shell
• Multilayer tablet

• Sugar coated tablets
• Protect tablets from moisture
• Mask odor and flavor
• Elegance

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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Types of tablets Production process

• Film coated tablets
• Thin film coat
• Soluble or insoluble polymer film

• Chewable tablets
• Rapid disintegrate
• Antacid, flatulance rapid action
• Children drug
• Effervescent tablets
• Dissolve in the water before drink

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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Ingredients used in tablet formulations

• Drugs
• Fillers, diluent, bulking agent
• To make a reasonably sized tablet
• Binders
• To bind powders together in the wet granulation
  process
• To bind granule together during compression
• Disintegrants
• To promote breakup of the tablets
• To promote rapid release of the drug

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
9
Ingredients used in tablet formulations (contd.)

• Lubricants
• To reduce the friction during tablet ejection
  between the walls of the tablet and the walls of
  the die cavity
• Glidants
• Reducing friction between the particles
• To improve the flow properties of the
  granulations
• Antiadherants
• To prevent adherence of the granules to the punch
  faces and dies

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
10
Ingredients used in tablet formulations (contd.)

• Dissolution (enhancers and retardants)
• Wetting agents
• Antioxidants
• Preservatives
• Coloring agents
• Flavoring agents

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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Essential properties of tablets

• Accurate dosage of medicament, uniform in weight,
  appearance and diameter
• Have the strength to withstand the rigors of
  mechanical shocks encountered in its production,
  packaging, shipping and dispensing
• Release the medicinal agents in the body in a
  predictable and reproducible manner
• Elegant product, acceptable size and shape
• Chemical and physical stabilities

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
12
Tablet production

• Powders intended for compression into tablets
  must possess two essential properties
• Powder fluidity
• The material can be transported through the
  hopper into the die
• To produce tablets of a consistent weight
• Powder flow can be improved mechanically by the
  use of vibrators, incorporate the glidant
• Powder compressibility
• The property of forming a stable, intact compact
  mass when pressure is applied

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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Tableting procedure

• Filling
• Compression
• Ejection

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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A Die filling B Compression C
Decompression D Lower punch removal and
reapplication of load to the upper punch E
Tablet fully ejected 1 refers to the final
compaction conditions
 Schematic diagram showing the manufacture of
single and bilayer tablets utilising uniaxial
compaction.
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WET GRANULATION DRY GRANULATION DIRECT COMPRESSION
1. Milling and mixing of drugs and excipients 1. Milling and mixing of drugs and excipients 1. Milling and mixing of drugs and excipients
2. Preparation of binder solution 2. Compression into slugs or roll compaction 2. Compression of tablet
3. Wet massing by addition of binder solution or granulating solvent 3. Milling and screening of slugs and compacted powder  
4. Screening of wet mass 4. Mixing with lubricant and disintegrant  
5. Drying of the wet granules 5. Compression of tablet  
6. Screening of dry granules    
7. Blending with lubricant and disintegrant to produce running powder    
8. Compression of tablet    
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Granulation
It is a process in which primary powder particles
are made to adhere to form larger, multiparticle
entities called granules. It is the process of
collecting particles together by creating bonds
between them. Bonds are formed by compression
or by using a binding agent.
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Granulation (contd.)

• The most common reasons given to justify
  granulating are
• To impart good flow properties to the material,
• To increase the apparent density of the powders,
• To change the particle size distribution,
• Uniform dispersion of active ingredient.

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Binders

• Used in tablet formulations to make powders more
  compressible and to produce tablets that are more
  resistant to breakage during handling.
• In some instances the binding agent imparts
  viscosity to the granulating solution so that
  transfer of fluid becomes difficult.
• This problem can be overcome by adding some or
  all binding agents in the dry powder prior to
  granulation.

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• Some granulation, when prepared in production
  sized equipment, take on a dough-like consistency
  and may have to be subdivided to a more granular
  and porous mass to facilitate drying.
• This can be accomplished by passing the wet mass
  through an oscillating type granulator with a
  suitably large screen or a hammer mill with
  either a suitably large screen or no screen at
  all.

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Oscillating type granulator
Hammer mill
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Drying

• The most common conventional method of drying a
  granulation continues to be the circulating hot
  air oven, which is heated by either steam or
  electricity.
• The important factor to consider as part of
  scale-up of an oven drying operation are airflow,
  air temperature, and the depth of the granulation
  on the trays.
• If the granulation bed is too deep or too dense,
  the drying process will be inefficient, and if
  soluble dyes are involved, migration of the dye
  to the surface of the granules.
• Drying times at specified temperatures and
  airflow rates must be established for each
  product, and for each particular oven load.

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• Fluidized bed dryers are an attractive
  alternative to the circulating hot air ovens.
• The important factor considered as part of scale
  up fluidized bed dryer are optimum loads, rate of
  airflow, inlet air temperature and humidity.

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Reduction of Particle size

• Compression factors that may be affected by the
  particle size distribution are flowability,
  compressibility, uniformity of tablet weight,
  content uniformity, tablet hardness, and tablet
  color uniformity.
• First step in this process is to determine the
  particle size distribution of granulation using a
  series of stacked sieves of decreasing mesh
  openings.
• Particle size reduction of the dried granulation
  of production size batches can be carried out by
  passing all the material through an oscillating
  granulator, a hammer mill, a mechanical sieving
  device, or in some cases, a screening device.

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Oscillating type granulator
Hammer mill
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Blending

• Type of blending equipment often differs from
  that using in laboratory.
• In any blending operation, both segregation and
  mixing occur simultaneously are a function of
  particle size, shape, hardness, and density, and
  of the dynamics of the mixing action.
• Particle abrasion is more likely to occur when
  high-shear mixers with spiral screws or blades
  are used.
• When a low dose active ingredient is to be
  blended it may be sandwiched between two portions
  of directly compressible excipients to avoid loss
  to the surface of the blender.

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• Equipments used for mixing
• Sigma blade mixer.
• Planetary mixer.
• Twin shell blender.
• High shear mixer

Planetary mixer
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Dry Granulation (slugging)

• A dry powder blend that cannot be directly
  compressed because of poor flow or compression
  properties.
• This is done on a tablet press designed for
  slugging, which operates at pressures of about 15
  tons, compared with a normal tablet press, which
  operates at pressure of 4 tons or less.
• Slugs range in diameter from 1 inch, for the more
  easily slugged material, to ¾ inch in diameter
  for materials that are more difficult to compress
  and require more pressure per unit area to yield
  satisfactory compacts.
• If an excessive amount of fine powder is
  generated during the milling operation the
  material must be screened fines recycled
  through the slugging operation.

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Dry Compaction

• Granulation by dry compaction can also be
  achieved by passing powders between two rollers
  that compact the material at pressure of up to 10
  tons per linear inch.
• Materials of very low density require roller
  compaction to achieve a bulk density sufficient
  to allow encapsulation or compression.
• One of the best examples of this process is the
  densification of aluminum hydroxide.
• Pilot plant personnel should determine whether
  the final drug blend or the active ingredient
  could be more efficiently processed in this
  manner than by conventional processing in order
  to produce a granulation with the required
  tabletting or encapsulation properties.

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Compression

• The ultimate test of a tablet formulation and
  granulation process is whether the granulation
  can be compressed on a high-speed tablet press.
• During compression, the tablet press performs the
  following functions
• Filling of empty die cavity with granulation.
• Precompression of granulation (optional).
• Compression of granules.
• Ejection of the tablet from the die cavity and
  take-off of compressed tablet.

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Tablet compression machines

• Hopper for holding and feeding granulation to be
  compressed
• Dies that define the size and shape of the tablet
• Punches for compressing the granulation within
  the dies
• Cam tracks for guiding the movement of the
  punches
• Feeding mechanisms for moving granulation from
  the hopper into the dies

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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Singe punch machine

• The compression is applied by the upper punch
• Stamping press

Source Assoc. Prof. Dr. Jomjai Peerapattana,
Faculty of Pharmaceutical Sciences, Khon Kaen
University
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Singe punch rotary machine
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Singe punch machine
Upper andLower Collar
Collar locker
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