Disintegrants

PHRM 210

Disintegrants

• The purpose of a disintegrant is to facilitate the breakup of a tablet when they contact water in gastrointestinal tract.

• A disintegrant is added to most tablet formulations to facilitate a breakup ordisintegration of the tablet when placed in an aqueous environment.

Disintegrants

• It should be noted that many disintegrants have also been shown to possess binder properties.

• Since disintegration is the opposite operation to granulation and the subsequent formation of strong compacts (tablets), one must carefully weigh these two phenomena when designing a tablet.

Disintegrants: MechanismBy capillary action (Wicking) :• Disintegrants may act by facilitating the

transport of liquids through the pores of the tablet and which weakens the intermolecular bond, as a results the tablet may break into fragments.

• Water uptake by tablet depends upon hydrophilicity of the drug /excipient and on tableting conditions.

Example: Microcrystalline cellulose (Avicel).

Disintegrants: MechanismBy swelling:• Rupturing of tablets can be caused by swelling

of the disintegrant particles by absorption of water.

• Tablets with high porosity may show poor disintegration due to lack of adequate swelling force. On the other hand, sufficient swelling force is exerted in the tablet with low porosity.

Disintegrants: MechanismBy swelling:• It is worthwhile to note that if the packing

fraction is very high, fluid is unable to penetrate in the tablet and disintegration is again slows down.

Example: Starch.

Wicking Swelling

Disintegrants: MechanismDue to deformation:• During tablet compression, disintegrant

particles get deformed and these deformed particles get into their normal structure when they come in contact with aqueous media or water.

• The swelling capacity of starch improved when granules were extensively deformed during compression.

Disintegrants: MechanismDue to deformation:• This increase in size of the deformed particles

produces a break up of the tablet. • This may be a mechanism of starch and has

only recently begun to be studied.

Disintegrants: MechanismDue to particle repulsive forces :• Nonswelling particle can also cause

disintegration of tablets. The electric repulsive forces between particles are the mechanism of disintegration and water is required for it.

• Researchers found that repulsion is secondary to wicking.

Factors affecting disintegration

Effects of fillers:• If soluble fillers are used then it may cause

increase in viscosity of the penetrating fluid which tends to reduce effectiveness of strongly swelling disintegrating agents and as they are water soluble, they are likely to dissolve rather than disintegrate.

• For example: Spray dried lactose

Factors affecting disintegration

• Insoluble diluents produce rapid disintegration with adequate amount of disintegrants.

• For example: Crystalline lactose monohydrate

Factors affecting disintegration

Effects of binders:• The major function of disintegrant is to

oppose the efficiency of the tablet binder.• The stronger the effect of the binder, the more

efficient must be the action of the disintegrating agents.

Factors affecting disintegration

Effects of lubricants:• Mostly lubricants are hydrophobic and they

are usually used in smaller size than any other ingredient in the tablet formulation. When the mixture is mixed, lubricant particles may adhere to the surface of the other particles. This hydrophobic coating inhibits the wetting and consequently tablet disintegration.

Disintegrants: Example

• Starch• Starch derivative• Clays• Cellulose• Alginates• PVP, Cross-linked

Disintegrants: Starch

• The most traditionally used disintegrant in conventional tablets is starch, among which potato, maize and corn starches are the most common types used.

• Starch form intermolecular hydrogen bonding during compression and is suddenly released in the presence of excess moisture.

Disintegrants: Starch

• Their efficiency as a disintegrate is due to its ability to swell 200 to 300 times in water without rapture of its granules.

• The typical concentration range of starch is 5-20% of tablet weight.

• Cost is very low.

Disintegrants: Microcrystalline cellulose

• Exhibit excellent disintegrant property when used in concentration as low as 10%.

• It functions by allowing water to enter the tablet matrix by means of capillary pores, which breaks the hydrogen bonds between microcrystalline cellulose.

Superdisintegrants

• Superdisintegrants which are effective at lowconcentration and have greater disintegrating efficiency.

• Have one drawback that it is hygroscopictherefore not used with moisture sensitive drugs.

Superdisintegrants

• Superdisintegrants act by swelling and due to swelling pressure exerted inthe outer direction or radial direction, it causes tablet to burst or theaccelerated absorption of water leading to an enormous increase in the volumeof granules to promote disintegration.

Superdisintegrants: Example

• Crosslinked cellulose• Crosslinked PVP• Crosslinked starch