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Intro into Tableting Part 1


Tablet presses – machines used to manufacture tablets.

Different parts of the tablet presses:

  • Wipe off blades – remove excess granulation
  • Turrets – holds the upper and lower punches

Direct Compression

  • Includes blending and compression
  • Tablets are compressed from excipients and powder API mixtures
  • Recommended for water sensitive and heat sensitive drugs
  • Has less step process
  • More economical


  • Static charge might build up during the mixing and screening which makes it difficult to align the drug distribution
  • Not recommended for low and high dose type of drugs
  • More costly and bulky as high dose drugs are not easily compressed without additional diluents
  • Mixing of drugs and direct compression diluents
  • Problem with the uniform distribution of the drug

Dry Granulation

Purpose – enlarging the tablet through conversion of particles into compressible granules

Dry granulation- the powder mix is compressed without using any solvent or heat in the process

2 methods of dry granulation:

  1. Slugging – the powder mixture is pre-compressed and the slug is milled further to be able to yield more granules.
    Slugging helps strengthen the bongs that makes friability free tablets.
  2. Roller compactation – it is used to produce granules in a bigger scale of which a Chillsonator roller is often used.
    Rollers are preferred as it increase production capacity and has more control over compactation pressure than slugging.


  • Uniformity of color distribution is not achieved
  • It requires a specific or special machine (Ex. Chilsonator)
  • Ideal method of precompression


Common diluents used for dry granulation:

  • Lactose
  • Calcium phosphate
  • Dextrose
  • MCC
  • sucrose
  • Sta-Rx (modified starch)

Wet Granulation

  • Granulation is facilitated by using a binder
  • Additives includes binder solution, slurry or suspension that is added to the powder mix
  • Most commonly used granulation method


  • Not ideal for moisture sensitive drugs
  • More expensive in terms of space, labor, energy and time

Drying process – helps remove the moisture and solvent from the wet granulation

Equipment use:

  1. High Shear
    • Littleford lodgie granulator
    • Gral mixer
    • Diosna granulator
    • Littleford lodgie MGT granulator
  2. Granulators that has drying facility
    • Fluidized bed granulator
    • Topo granulator
    • Double cone or twin shell processor
    • Day nauta mixer processor
  3. Special
    • Roto granulator
    • Marumerizer


Lactose – most commonly used excipient in the production of tablets

Anhydrous lactose – do not undergo Maillard reaction when combined with amine drugs

Maillard Reaction – it is a reaction between amino acids and reducing sugar

2 grades of lactose:

  • 60-80 mesh (coarse)
  • 80-100 mesh (regular grade)

*When spray dried lactose are expose to amine and moisture, it darkens. This is due to the presence of Furaldehyde.

Diluents – Lactose

Sta-Rx 1500 – it is a directly compressible starch

  • Used as a diluent, disintegrating agent and as a binder
  • Contains 10% water

Hydrolyzed starch – both examples below contains 90-92% dextrose, 3-5% maltose

  • Embdex
  • Celutab

Dextrose – Cerelose

Mannitol – used for chewable tablets, generally an expensive sugar type. It needs huge quantity of lubricants due to its poor flow characteristics.

Sugar/sucrose – it can be used as direct compressible diluent

  • Sugar tab: 90-93% sugar + 7-10 % invert sugar
  • Nutab: 95% sugar + 4% invert sugar with corn starch and magnesium stearate
  • Dipac: 97% sugar + 3% dextrins

Avicel - Micocrystalline cellulose

Two grades:

  • PH101 for powders: 50 um particle size
  • PH102 for granules: 100 um particle size

Binders - to form the granules

  • Natural binders
  • Starch paste
  • Acacia
  • Gelatin
  • Tragacanth
  • Cellulose
  • Alginic paste
  • Synthetic
  • Methyl cellulose
    • Ethyl cellulose
    • Sodium carboxymethly cellulose
    • PVP
    • HPMC
    • PEG
    • Hydroxyl methyl cellulose

Commonly Used Binders

  • Walocel- Hydroxy propyl methyl cellulose
  • Starch 1500 - Partially pregelatinized maize starch
  • Methocel-HPMC
  • Sugar


Disintegrants are used to help tablets disintegrate in the GI tracts


  • Starch- 5-20% of tablet weight
  • Clays- Veegum HV, bentonite 10% level in colored tablet only
  • Starch derivative - Primogel and Explotab (1-8%)
  • Cellulose derivatives- Ac- Di-Sol (sodium carboxy methyl cellulose)
  • Other: cross-linked Polyvinylpyrrolidone

Superdisintegrants – when expose to water in 30 minutes would swell up to 10x its normal size


  • Cross carmellose: cross linked cellulose
  • Sodium starch glycolate: cross linked starch
  • Ethyl cellulose (may retard disintegration and dissolution time of tablet)
  • Cross povidone: cross linked povidone


Lubricants – are used to reduce friction between the tablet’s surface and the die/molds during the ejection process.

Anti-adherents – are used to prevent the granules or powder from sticking to the dies and punches

Glidants – it helps improve the flow properties of the granules by reducing the friction

Example of Common Lubricants:

  • Stearic acid and stearic acid salts such as calcium and magnesium salts
  • Stearic acid is less effective lubricant than its salts
  • High molecular weight PEG
  • Talc- second most commonly used
  • Surfactants
  • Hydrocarbon oils

Example of Anti-adherents

  • Talc
  • Colloidal silica
  • Mag stearate
  • Starch

Example of Glidants/flow promoters

  • Talc (5%)
  • 0.25-3% conc
  • Starch (5-10%)
  • Aerosil
  • Colloidal silica: Cab-o-sil
  • Syloid

Colors – Lakes – are dry powders that are absorbed by hydrous oxide and are used to add color to the tablet.

Flavors – Chewable Tables

Sweetening Agents

  • Aspartame – high instability in water
  • Saccharine – 500x times more sweeter than sucrose, has bitter after taste, carcinogenic

Processing Challenges:

Capping – happens when there is a partial separation of the upper and lower area of the tablet

Lamination – when the tablet separates into several layers (cause by the air entrapped in the granules)


  • Reducing the final compression pressure
  • Precompression
  • Lesser moisture in granules (capping), increase the binder (lamination)
  • Correcting the settings of the machine
  • Using flat punches which can prevent lamination or capping
  • Slowing the tableting rate

Picking and Sticking

  • Picking – happens when the granules sticks to the punches
  • Sticking – happens when the granules sticks to the punch instead of creating a uniform tablet

Chipping – happens when there are severe sticking in the punches resulting to tablets that has rough edges


  • Reduction of excess moisture in the granules
  • Using large embossing or engraving
  • Using of lubricants
  • Usage of chromium plated punch to produce a smooth tablet surface
  • Checking of low molecular weight lubricants added as the components may melt when expose to heat of the compression

Mottling – when there is unequal color distribution among the tablets processed.


  • Use of different binders such as tragacanth or acacia
  • Lowering the drying temperature
  • Reduction of the particle size of the powder
  • Change in the solvent system use

Poor Flow – happens when there is bridging or rat holing in the feeding frame. To improve flowability, the use of glidants such as colloidal silica or talc is recommended.

Double Compression – happens when there is a free rotation of the lower or upper punches during the ejection period of the tablet.

To prevent punch rotation, keying in tooling is used. New machines have anti-turning devices that prevents the punches to rotate freely.