SUPERDISINTEGRANTS

by [Link] (Reg no.08CC1R0045)

Guidance of [Link] Kumar

MRR

COLLEGE OF [Link] JNTU HYDERABAD NADERGUL,SAROORNAGAR [Link]

INTRODUCTION
Disintegrants are agents added to tablet (and some encapsulated) formulations to promote the
breakup of the tablet and capsule slugs into smaller fragments in an aqueous environment thereby increasing the available surface area and promoting a more rapid release of the drug substance. Tablet disintegration has received considerable attention as an essential step in obtaining fast drug release. The disintegrants have the major function to oppose the efficiency of the tablet binder and the physical forces that act under compression to form the tablet. The ability to interact strongly with water is essential to disintegrate function. Combinations of swelling and/or wicking and/or deformation are the mechanisms of disintegrate action. A disintegrate used in granulated formulation processes can be more effective if used both intra-granularly and extra granularly there by acting to break the tablet up into granules and having the granules further disintegrate to release the drug substance into solution. However, the portion of disintegrate added intragranularly (in wet granulation processes) is usually not as effective as that added extra granularly due to the fact that it is exposed to wetting and drying (as part of the granulation process) which reduces the activity of the disintegrate.

THERE ARE THREE METHODS OF INCORPORATING DISINTEGRATING AGENTS INTO THE TABLET:
A.

Internal Addition (Intra-granular)

B.

External Addition (Extra granular)

C.

Partly Internal and External.

DISINTEGRATES

Disintegrates are agents added to tablet and some encapsulated formulations to promote the breakup of the tablet and capsule slugs into smaller fragments in an aqueous environment there by increasing the available surface area and promoting a more rapid release of the drug substance.

EXAMPLES:[Link] Starches

Sodium Carboxymethyl Starch i.e. Sodium Starch Glycolate (Explotab, Primogel) Mechanism of Action: Rapid and extensive swelling with minimal gelling. Effective Concentration: 4-6%. Above 8%, disintegration times may actually increase due to gelling and its subsequent viscosity producing effects.

[Link]-linked polyvinyl pyrrolidoneThese are Water insoluble and strongly [Link](Polyplasdone XL, Kollidon CL) Mechanism of Action: Water wicking, swelling and possibly some deformation recovery. Effective Concentration:2-4%

3. Modified CelluloseInternally cross-linked form of Sodium carboxymethyl cellulose.i.e. Ac-Di-Sol (Accelerates Dissolution), Nymcel Mechanism of Action: Wicking due to fibrous structure, swelling with minimal gelling. Effective Concentrations: 1-3% (Direct Compression), 2-4% (Wet Granulation)

ADVANTAGES:

Effective in lower concentrations than starch Less effect on compressibility and flow ability More effective intragranularly

DISADVANTAGES:

More hygroscopic (may be a problem with moisture sensitive drugs)

Superdisintegr ans
Crosslinked cellulose

Commerciallya va lable Grade

Mechanism of action
Swells 4-8 folds in < 10 seconds. Swelling and wicking bot

Special comment
Swells in two dimensions. Direct compression or

Vivasol, L-HPC
Crosslinked PVP Crosspovidon Mkollidon Polyplasdone Swells very little and returns to original size after compression but act by capillary action Crosslinked starch Explotab Primogel Swells 7-12 folds in < 30 Seconds

Granulation Starch Free

Swells in three dimensions and high level serve as sustain release matrix

Crosslinked alginic Acid

Alginic acid NF

Swells 7-12 folds in < 30 Second

Swells in three dimensions and high level serve as sustain release matrix

Soy polysaccharides

Emcosoy

Does not contain any starch or Sugar. Used

in nutritional products
Calcium silicate Wicking action. Highly porous,Light weight,

MECHANISM:
There are three major mechanisms and factors affecting tablet disintegration as follows:

Swelling Porosity and Capillary Action (Wicking) Deformation

Swelling

Although not all effective disintegrants swell in contact with water, swelling is believed to be a mechanism in which certain disintegrating agents (such as starch) impart the disintegrating effect. By swelling in contact with water, the adhesiveness of other ingredients in a tablet is overcome causing the tablet to fall apart.

Porosity and Capillary Action (Wicking)

Effective disintegrants that do not swell are believed to impart their disintegrating action through porosity and capillary action. Tablet porosity provides pathways for the penetration of fluid into tablets. The disintegrant particles (with low cohesiveness & compressibility) themselves act to enhance porosity and provide these pathways into the tablet. Liquid is drawn up or wicked into these pathways through capillary action and rupture the interparticulate bonds causing the tablet to break apart.

Deformation

Starch grains are generally thought to be elastic in nature meaning that grains that are deformed under pressure will return to their original shape when that pressure is removed. But, with the compression forces involved in tableting, these grains are believed to be deformed more permanently and are said to be energy rich with this energy being released upon exposure to water. In other words, the ability for starch to swell is higher in energy rich starch grains than it is for starch grains that have not been deformed under pressure.

FACTORS WHICH AFFECT THE DISSOLUTION OF DRUGS FROM TABLETS ARE:

Type and Concentration of Active Ingredient

SUPER DISINTEGRATION EFFICIENCY

Polyplasdone crospovidone quickly wicks saliva into the tablet to generate the volume expansion and hydrostatic pressures necessary to provide rapid disintegration in the mouth. Unlike other superdisintegrants, which rely principally on swelling for disintegration, Polyplasdone superdisintegrants use a combination of swelling and wicking

APPLICATIONS

Crospovidone is one of the three superdisintegrants described in the literature. The mechanism of action is a capillary action with a secondary swelling effect. The improvement of tablet disintegration also has been observed through predictable swelling without gel formation. Crospovidone is a disintegrating agent at the 25% level and is an effective binderdisintegrant in tablets prepared using wet granulation. Furthermore, swelling properties paired with particle-size distribution make the finer grades of crospovidone work efficiently in fast-disintegrating formulations.

DISINTEGRATION TEST FOR TABLETS DOSAGE FORM:

Uncoated Tablets Coated Tablets Enteric-coated Tablets Effervescent Tablets Film-coated tablets

Sugar-coated Tablets

DOSAGE FORM:

Uncoated Tablets: -Comply with the disintegration test for tablets and capsules,. Unless
otherwise directed in the individual monograph, use water as the medium and add a disc to each tube. Operate the apparatus for 15 minutes unless otherwise directed.

Coated Tablets: -Comply with the disintegration test for tablets and capsules,. Unless
otherwise directed in the individual monograph, use water as the medium and add a disc to each tube. Operate the apparatus for 30 minutes for film-coated tablets and for 60 minutes for other coated tablets unless otherwise directed in the individual monograph. For coated tablets other than film-coated tablets, if any of the tablets have not disintegrated, repeat the test on a further 6 tablets, replacing the water in the vessel with 0.1M hydrochloric acid. The tablets comply with the test if all 6 tablets have disintegrated in the acid medium.

Enteric-coated Tablets:-Comply with the disintegration test for tablets and capsules,. If
the tablet has a soluble external coating, immerse the basket in water at room temperature for 5 minutes. Suspend the assembly in the beaker containing 0.1M hydrochloric acid and operate without the discs for 120 minutes, unless otherwise stated in the individual monograph. Remove the assembly from the liquid. No tablet shows signs of cracks that would allow the escape of the contents of disintegration, apart from fragments of coating. Replace the liquid in the beaker with mixed phosphate buffer pH 6.8, add a disc to each tube and operate the apparatus for a further 60 minutes. Remove the assembly from the liquid. The tablets pass the test if all six have disintegrated. Dispersible and Soluble Tablets: Disintegrate within 3 minutes when examined by the disintegration test for tablets and capsules, using water at 24o to 26o, unless otherwise stated in the individual monograph.

Effervescent Tablets:- Place one tablet in a 250-ml beaker containing water at 20o to
30o; numerous gas bubbles are evolved. When the evolution of gas around the tablet or its fragments has ceased the tablet shall have disintegrated, being either dissolved or dispersed in the water so that no agglomerates of particles remain. Repeat the operation on a further 5 tablets. The tablets comply with the test if each of the 6 tablets disintegrates in the manner prescribed within 5 minutes, unless otherwise stated in the individual monograph.

Sugar-coated tablets:- sugar-coated tablets comply with 5.3 Disintegration test for
tablets and capsules. Operate the apparatus for 60 minutes, unless otherwise specified in the individual monograph, using water, and examine the state of the tablets. If any of the tablets has not disintegrated, repeat the test on an additional six tablets, using hydrochloric acid (0.1 mol/l) VS.

Film-coated tablets :-Film-coated tablets comply with 5.3 Disintegration test for tablets
and capsules. Operate the apparatus for 30 minutes, and examine the state of the tablets.

EVALUTION ASPECTS OF SUPERDISINTEGRANTS

Most common tablets are those intended to be swallowed wholeband to disintegrate and release their medicaments rapidly in the gastrointestinal tract (GIT). The proper choice of disintegrant and its consistency of performance are of critical importance to the formulation development of such tablets. In more recent years, increasing attention has been paid to formulation not only fast dissolving and/or disintegrate rapidly in the month. Most prior studieshave focused on the function-related properties of superintegrants with special emphasis on correlating these functional properties to disintegrant efficiency and drug release rate. Water penetration rate of disintegration force development are generally positively related to disintegrant efficiency in non-soluble matrices. However, such a positive correlation is not always observed between tablet disintegration time and drug dissolution rate.

CONCLUSION

The study compared various superdisintegrants in terms of physicochemical properties and use in direct compression and compression after wet granulation. Polyplasdone XL and Kollidon CL displayed obvious differences in various parameters. The particle-size distribution of Polyplasdone XL is broader, and the swelling volume is bigger than those of Kollidon CL. Kollidon CL-F and SF grades had a substantially smaller particle size than Kollidon CL and Polyplasdone XL and showed higher swelling volumes and hydration capacities. In contrast to crospovidone, Ac-Di-Sol and Primojel generate a gel-like consistency upon contact with water, causing high swelling volume and medium-to-high swelling pressure. The disintegration effect should be correlated with particle size. This study indicated that a combination of various properties, including swelling pressure and volume, hydration capacity, and swelling behavior create a good disintegrant.