SUPER DISINTEGRANTS: A REVIEW

Recently new materials termed as “super disintegrants” have been developed to improve the disintegration processes. Super disintegrants are another version of super-absorbing materials with tailor-made swelling properties.

The prevalent use of Superdisintegrants in orally and fast integrating tablets along with the adoption of new drug delivery system technologies are some other factors propelling the market growth.

It shows the superdisintegrants market growth from 2014 to the forecast period 2025.

The inclusion of the right super disintegrant is a prerequisite to get optimal bioavailability in tablets and capsules which need rapid disintegration. Super disintegrants are used to improve the efficacy of solid dosage forms. This is achieved by decreasing the disintegration time which in turn enhances the drug dissolution rate.

Factors such as growing generic drugs market, geriatric and paediatric population who have difficulty in swallowing tablet/capsules and development of new superdisintegrants for the pharmaceutical industry is driving the growth of the market.

Types of Superdisintegrants

• Synthetic Superdisintegrants 

                          Croscarmellose Sodium

                          Crospovidone

                          Sodium starch glycolate

                          Ion exchange resin

• Others

 

CROSCARMELLOSE SODIUM

Croscarmellose sodium is a product of the alkali-catalyzed reaction of cellulose with sodium monochloroacetate under rigidly controlled conditions. CCS is cross-linked carboxymethylcellulose sodium and used as a pharmaceutical additive approved by the US Food and Drug Administration. It is used in wordwide as a superdisintegrant in pharmaceuticals and dietary supplements. It is a natural product that is free of sugar and starch.CCS is hydrophilic, but, made insoluble and fibrous by cross-linking of sodium salt of carboxymethylcellulose. The functionality of CCS as a superdisintegrant is related to its fluid uptake and swellability characteristics. Swelling, wicking, and strain recovery are proposed mechanisms for CCS. Because swelling of CCS is attributed to the hydration of the carboxymethyl group, the degree of substitution determines CCS functionality.

Particle size, degree of substitution, and the ratio of acidic to basic substituents are major factors influencing the swelling of CCS.  The carboxymethyl substitution increases the swelling ability of CCS, with basic substituents having a better tendency to swell than acidic. A larger particle size of CCS leads to enhanced swelling and faster disintegration because CCS forms a viscous layer upon contact with water, and a smaller particle size forms a more viscous layer because of enhanced interactions with water.

Concentration

It is used in the range of 0.5%–5% w/w but up to 2% is sufficient in most formulation prepared by direct compression and 3% when tablets prepared by a wet-granulation process.

SODIUM STARCH GLYCOLATE 

Sodium Starch Glycolate is the sodium salt of a carboxymethyl ether of starch. These are modified starches made by crosslinking of potato starch as it gives the product with the best disintegrating properties. The degree of cross-linking and substitution are important factors in determining the effectiveness of these materials as super disintegrants. The effect of the crosslinking is to reduce both the water-soluble fraction of the polymer and the viscosity of dispersion in water.

Concentration

It is used in the range of 2-8%. Above 8%, disintegration times may actually increase due to gelling and its subsequent viscosity producing effects.

CROSPOVIDONE (CROSS-LINKED POLYVINYL PYRROLIDONE)

Unlike other super disintegrants, which rely principally on swelling for disintegration, crospovidone use a combination of swelling and wicking. Due to its high crosslink density, crospovidone swells rapidly in water without gelling. Crospovidone particles are found to be granular and highly porous which facilitates wicking of liquid into the tablet and particles to generate rapid disintegration. Larger particles provide a faster disintegration than smaller particles. Crospovidone disintegrants are highly compressible materials as a result of their unique particle morphology.Crospovidone can also be used as solubility enhancer.

Crospovidone has the ability to stabilize the amorphous state of drugs due to inhibition of drug recrystallization and a rapid solidification rate. In addition, crospovidone has excellent disintegration and dissolution enhancing effect, which is usually used in the preparation of tablets, granules, and capsules.

Concentration

It is used in the range of 2%–5% w/w. Concentration range up to3% gives better results. Crospovidone levels higher than 8% of tablet weight produces weaker tablets with a faster disintegration.

ION EXCHANGE RESINS

Ion exchange resins are water insoluble cross-linked polymers containing a salt-forming group at repeating positions on the polymer chain. They can be classified as cationic or anionic exchange resins depending upon the nature of the exchangeable ion of the resin as a cation or anion, respectively. The degree of cross-linking and particle size of the resin substantially modify its properties and applications. Ion exchange resins can be used to overcome various pharmaceutical formulation problems including bitter taste, poor stability, deliquescence, and poor dissolution of the drugs. Resins have also been used as superdisintegrants in tablet formulations because of their swelling properties. Because of the versatile utility of ion exchange resins, they are being used for various drug delivery and therapeutic applications.

The advantages of ion exchange resins as superdisintegrants as compared to conventional ones are that they swell on getting hydrated but do not dissolve or have an adhesive tendency, a feature commonly encountered with gums. Thus, the tablet disintegrates evenly. Ion exchange resins are efficient at considerably lower levels than recommended for conventional disintegrants.

Example of cationic exchange resin, Polacrilin potassium is a monofunctional minimally cross-linked carboxylic acid-exchange resin prepared by the co-polymerisation of methacrylic acid with divinylbenzene and subsequently neutralised with potassium hydroxide.  Polacrilin potassium is an efficient disintegrant in low concentration in various tablet formulations, including many hydrophobic formulations where standard disintegrants are poorly effective. It is weakly acidic cation exchange resin. On wetting, the resin swells by approximately 150%, thereby causing the tablet to disintegrate. Tablet disintegration property is due to its extremely large swelling capacity in aqueous solutions. Water can exert force between particles within tablet pores, but this force is low. It is bio-compatible and non-toxic. It is available in various grades.

Concentration

Concentration range 1-2% gives better results.

OTHERS

However, the others segment which includes natural superdisintegrants such as Isapghula husk, gellan gum, and locust bean gum is expected to grow at the highest during the forecast period. It has instant swelling features when it comes into contact with water due to its high hydrophilic nature, which results in the rapid disintegration of tablets. Apart from these superdisintegrants, researchers are continuously investigating novel disintegrating agents. It includes testing of modified natural products, such as chitin, chitosan, polymerized agar acrylamide, xylem, cross-linked carboxymethyl guar, and modified tapioca starch.

CHARACTERISTICS

Super disintegrants	Croscarmellose  sodium	Sodium starch glycolate	Crospovidone	Polacrilin potassium
Mechanism	Swelling and wicking both. Swells 4-8 folds in <10 seconds.	Swelling and wicking bothSwells 6-10 folds in <30 seconds	Swelling and wicking both. Swells 7-12 folds in <30 seconds	Swelling and wicking both.
Incompatibilities	Incompatible with strong acids or with soluble salts of iron and some other metals such as aluminum, mercury, and zinc.	Incompatible with ascorbic acid	Forms molecular adducts in solution with sulfathiazole, sodium salicylate, salicylic acid, phenobarbital, tannin, and other compounds	Incompatible with strong oxidising agents, amines, particularly tertiary amines, and sone other substances that interact with polac rilin resins.
Gel Forming Tendency	Yes	Yes	No	Yes

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About the Author:

Dr. Ajay Kumar Singh, M.Sc. (Gold Medalist), Ph.D. is the author and founder of “Pharma Solutions by Dr. Ajay”.

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