In the part 2 of this module, we will learn the following on the tablets. In this module, we will study only important points for NIPER JEE. Kindly read the references given at the end, if you need more comprehensive information on any topic.
Machines used to manufacture tablets are called tablet presses.
Roles of different parts of tablet presses
Turrets: It holds the upper and lower punches
Wipe off blades: To remove excess granulation
Used for the production of suppositories.
Used for the compression of low melting point substances such as waxes
* Tablets compressed directly from powder mixture of API and excipients
* It involves blending and compression steps
* Have lesser steps
* Suitable for heat and water sensitive drugs
* Economical and cheaper technology
* Not suitable for low and high dose drugs
* High dose drugs may not be directly compressible - to make them compressible large amount of diluents is required making them bulky and costly
* Low dose drugs- problems in uniform distribution of drug
* Interaction of direct compression diluents and drugs
* A static charge sometime buildup during mixing and screening process which further make the uniform distribution of drug a challenge.
Purpose of granulation: size enlargement process which converts particles into large free flowing and compressible granules
Dry granulation- powder mixture is compressed without the use of heat and solvent
Two methods for dry granulation
Slugging: powder is pre-compressed and slug is further milled to yield the granules.
Purpose of slugging
Slugging results in strengthening of bongs that make friability free tablets
It is used to produce granules on larger scale
Chilsonator roller is most commonly used
Rollar compression is generally preferred method over slugging method due to increased production capacity and greater control over compactation pressure.
Advantages of dry granulation
* Suitable for moisture sensitive and heat sensitive drugs
* Improved disintegration time as binder is not used in dry granulation
Disadvantage of dry granulation
Requires a specialized machine for precompression such as chilsonater
Uniform color distribution can't be achieved
Preferred method of precompression
Formulation for dry granulation
The commonly used diluents are:
Sta-Rx (modified starch)
* Most widely used method of granulation
* The granulation is facilitated by a binder
* Wet granuation involves addition of binder solution, suspension or slurry to the powder mixture
* Costly process because of labor, time, equipment, energy and space requirements.
* Not suitable for moisture sensitive drugs
Role of drying process
To remove the solvents and moisture used in wet granulation
List of equipments for wet granulation
High shear granuation
* Littleford lodgie granulator
* Littleford lodgie MGT granulator
* Diosna granulator
* Gral mixer
Granulator with drying facility
* Fluidized bed granulator
* Day nauta mixer processor
* Double cone or twin shell processor
* Topo granulator
* Roto granulator
Lactose is most widely used in tablet production
Anhydrous lactose does not undergo Maillard reaction with amine drugs
Maillard reaction: reaction between amino acids and reducing sugar
Two grades of lactose:
60-80 mesh (coarse)
80-100 mesh (regular grade)
Spray dried lactose darkens in presence of amine and moisture due to the presence of Furaldehyde
Sta-Rx 1500- directly compressible starch
* Used as diuent, binder and disintegrating agent
* Contain 10% water
* Both contain 90-92% dextrose and 3-5% maltose
* Expensive sugar
* Suitable for chewable tablets
* Poor flow characteristics- need large amount of lubricants
Sucrose or sugar - used as direct compressible diluent
* Sugar tab: 90-93% sugar + 7-10 % invert sugar
* Dipac: 97% sugar + 3% dextrins
* Nutab: 95% sugar + 4% invert sugar with corn starch and magnesium stearate
Avicel : Micocrystalline cellulose
PH101 for powders: 50 um particle size
PH102 for granules: 100 um particle size
To form the granules
* Starch paste
* Alginic paste
* Methyl cellulose
* Ethyl cellulose
* Hydroxyl methyl cellulose
* Sodium carboxymethly cellulose
Commonly used binders
* Starch 1500 - Partially pregelatinized maize starch
* Walocel- Hydroxy propyl methyl cellulose
* Sugar is also used as binders
They cause disintegration of tablets in GI tracts
Example: Starch- 5-20% of tablet weight
Starch derivative - Primogel and Explotab (1-8%)
Clays- Veegum HV, bentonite 10% level in colored tablet only
Cellulose derivatives- Ac- Di-Sol (sodium carboxy methyl cellulose)
Other: cross-linked Polyvinylpyrrolidone
Swells 10 times of their size in water in 30 sec
Cross carmellose: cross linked cellulose
Cross povidone: cross linked povidone
Sodium starch glycolate: cross linked starch
Ethyl cellulose may retard disintegration and dissolution time of tablet
Lubricants, anti-adherents and glidants
Lubricants: decrease the friction between walls of tablet and die cavity during ejection process
Anti-adherents: decrease the sticking of granule or powder to the punches and dies
Glidants: increase the flow properties of granules by decreasing the friction
Most commonly used lubricants
* Stearic acid and stearic acid salts such as calcium and magnesium salts
* Stearic acid is less effective lubricant than its salts
* Talc- second most commonly used
* Hydrocarbon oils
* High molecular weight PEG
* Mag stearate
* Colloidal silica
* Talc (5%)
* Starch (5-10%)
* Colloidal silica: Cab-o-sil
* 0.25-3% conc
Lakes: dyes absorbed on hydrous oxides and used as dry powders for coloring
For chewable tablets
Saccharine- 500 times sweeter than sucrose
Disadvantage: bitter after taste and carcinogenic
Aspartame: Unstable in water
Capping: it is complete or partial separation of upper or lower layers of tablets.
Lamination: it is separation of tablets into multiple layers.
Reason: due to entrapment of air in granules.
* Slowing the tabletting rate
* Reducing the final compression pressure
* Flat punches may prevent the capping and lamination
* Less moisture in granules result in capping and lamination-increase the amount of binder
* Correcting the incorrect setting of tools of press such as dies, punches and sweep-off blades
Picking and sticking
Sticking is when the granules are sticked to the punches instead of creating a uniform tablet.
Picking occurs when the granules or tablet sticks to the engraving or embossing on the punches.
Small enclosed alphabets such as B, A, O, D, Q on punches pose special challenges in producing a sticking free tablet.
Chipping: due to severe sticking of material at the punches, produces tablets with rough edges.
* Alphabets can be designed as large as possible
* Chromium plated punches to produce a smooth surface
* Use of lubricants such as silica, magnesium stearate
* Low molecular weight lubricants such as polyethylene glycol , stearic acid may promote sticking as they melt due heat of compression
* Reducing the excessive moisture in granules
Unequal distribution of color in a tablet.
* Change in solvent system
* Reducing drying temperature
* Reducing particle size of powders
* Using of binders such as acacia and tragacanth
Rat holing and bridging in the feed frame. The flow of powder in feed frame can be increased by using glidants such as talc or colloidal silica.
* Free rotation of either upper punch or lower punch during ejection of a tablet.
* Use keying in tooling, i.e. inset a key alongside of the punch, so that it fits the punch and prevents punch rotation.
* Newer presses have anti-turning devices, which prevent punch rotation.
References and further reading
Banker, G. S., & Anderson, N. R. (1991). The theory and practice of industrial pharmacy; Lachman, L. 3rd edition.
Remington, J. P. (2006). Remington: The science and practice of pharmacy (Vol. 1). D. B. Troy, & P. Beringer (Eds.). Lippincott Williams & Wilkins.