INTRODUCTION:

Oral route of drug administration is perhaps the most appealing route for the delivery of drugs. Various dosage forms administered orally, the tablet is one of the most preferred dosage forms amongst them because of its ease of manufacturing, convenience in administration, accurate dosing, and stability compared with oral liquids and because it is more tamperproof than capsules. The bioavailability of drug is dependent on in vivo disintegration, dissolution, and various physiological factors[1]. Tablet disintegration has received considerable attention as an essential step in obtaining fast drug release. The emphasis on the availability of drug highlights the importance of the relatively rapid disintegration of a tablet as a criterion for ensuring uninhibited drug dissolution behaviour[2].

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. They promote moisture penetration and dispersion of the tablet matrix. A disintegrant used in granulated formulation processes can be more effective if used both “intragranularly” and “extragranularly” thereby acting to break the tablet up into granules and having the granules further disintegrate to release the drug substance into solution. Most common tablets are those intended to be swallowed whole and 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 [3] In more recent years, increasing attention has been paid to formulating not only fast dissolving and/or disintegrating tablets that are swallowed, but also orally disintegrating tablets that are intended to dissolve and/or disintegrate rapidly in the mouth. The task of developing rapidly disintegrating tablets is accomplished by using a suitable superdisintegrants [4].

In recent years several newer agents have been developed known as “Superdisintegrants”. These newer substances are more effective at lower concentrations with greater disintegrating efficiency and mechanical strength. Water penetration rate and 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. [5] Superdisintegrants provide quick disintegration due to combined effect of swelling and water absorption by the formulation. Due to swelling of superdisintegrants, the wetted surface of the carrier increases, which promotes the wettability and dispersibility of the system, thus enhancing the disintegration and dissolution.[6] Effective superdisintegrants provide improved compressibility, compatibility and have no negative impact on the mechanical strength of formulations containing high-dose drugs. Number of factors affects the disintegration behaviour of tablets. The optimum concentration of the superdisintegrant can be selected according to critical concentration of disintegrant. The ability to interact strongly with water is essential to disintegrant function. Combinations of swelling and/or wicking and/or deformation are the mechanisms of disintegrant action. 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.[7]

MECHANISM OF ACTION:

1. By Swelling Action

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 fall apart [8] as in figure 1. eg : Sodium starch glycolate.

4. By Electrostatic Repulsion

Guyot-Hermannet et al., has proposed a particle repulsion theory based on the observation that non swelling particle also cause disintegration of tablets. The electric repulsive forces between particles are the mechanism of disintegration and water is required for it show in figure 4 [10]

Methods of Incorporating Disintegrants into Tablets:

There are two methods of incorporating disintegrating agents into the tablet as described below

1. Internal Addition (Intragranular):

In Internal addition method, the disintegrant is mixed with other powders before wetting the powder mixtures with the granulating fluid. Thus the disintegrant is incorporated within the granules.

2. External Addition (Extragranular):

In external addition method, the disintegrant is added to the sized granulation with mixing prior to compression.

3. Partly Internal and External:

In this method, part of disintegrant can be added internally and part externally. This results in immediate disruption of the tablet into previously compressed granules while the disintegrating agent within the granules produces additional erosion of the granules to the original powder particles [11,12 13]

They all should possess the following characteristics:

1. Poor water solubility with good hydration capacity,

2. Poor gel formation,

3. Good flow properties

4. Good compressibility,

5. Inert,

6. Non-toxic,

7. Requirement of least quantity

Table.1. Parameters influencing the swelling behaviour of Superdisintegrants

Parameters	Effects
Amount of superdisintegrant	A minimum amount of superdisintegrant is necessary for the development of sufficient swelling to outer membrane
Additives (binders)	Polymeric binders can reduce swelling pressure by spacial separation of superdisintegrant particles or competition for free water
Ionic strength of the medium	Competition of the ions for free water
ph values	Swelling can be influenced for the superdisintegrants with ionizable groups (e.g:carboxylic groups in croscarmellose )

TYPES OF SUPERDISINTEGRANTS:

1. Cross-linked poly-vinyl Pyrrolidone (Cross Povidone) :

In case of mouth-dissolving formulations, Crospovidone quickly wicks saliva into them to generate the volume expansion and hydrostatic pressures necessary to provide rapid disintegration in the mouth. Unlike other superdisintegrants, it relies on both swelling and wicking principally for disintegration. When examined under a scanning electron microscope, crospovidone particles appear to be granular and highly porous. This unique, porous nature facilitates wicking of liquid into the dosage systems and causes rapid disintegration. Due to high crosslink density of crospovidone, it swells rapidly in water without gel formation than others [14]. In contrast to other superdisintegrants like sodium starch glycolate and croscarmellose sodium, Crospovidone exhibit virtually no tendency toward gel formation, even at high ratio. As disintegrants that result gel formation is not appreciable in orally disintegrating tablets (ODTs) and chewable products.

2. Crosscarmellose Sodium (Modified cellulose):

It is modified cellulose and is a cross linked polymer of carboxymethylcellulose. The disintegration rate of crosscarmellose sodium is higher than that of sodium starch glycolate and the mechanism is also different. The carboxymethyl groups themselves are used to cross link the cellulose chains, process is accomplished by dehydration. The substitution is performed by using Williamson’s ether synthesis to give the sodium salt of carboxymethyl cellulose. Thus the crosslinks are carboxyl ester links rather than phosphate ester links as in Primojel. Cross linking makes it insoluble, hydrophilic, highly absorbent material, resulting in excellent swelling properties and its unique fibrous nature gives it excellent water wicking capabilities. It is used in oral pharmaceutical formulations as a superdisintegrant for capsules, tablets and granules. Concentrations of croscarmellose sodium range between 1-5% w/w, although normally 1-3% w/w is used in tablets prepared by direct compression and 2- 4% w/w in tablets prepared by a wet granulation process. Botzolakis et al.19 have studied the wicking and swelling properties of pure superdisintegrants from the plugs which are prepared under condition similar to those used in encapsulation of powder mixture into hard gelatin capsules [15].

3. Modified Starches:

Sodium Carboxymethyl Starch (Sodium Starch Glycolate)It is possible to synthesize sodium starch glycolate from a wide range of native starches, but in practice potato starch is used as it gives the product with the best disintegrating properties. After selection of the appropriate starch source the second step is the crosslinkingof the potato starch. This is typically carried out using an FDA approved starch esterifying agent such as sodium trimetaphosphate or phosphorus oxychloride in alkaline suspension. The effect of introduction of the large hydrophilic carboxymethyl groups is to disrupt the hydrogen bonding within the polymer structure. This allows water to penetrate the molecule and the polymer becomes cold water soluble. The effect of the crosslinking is to reduce both the water soluble fraction of the polymer and the viscosity of dispersion in water. The optimum balance between the degree of substitution and the extent of cross-linking allows for rapid water uptake by the polymer without the formation of a viscous gel that might impede dissolution [16-17].

4. Microcrystalline Cellulose (Avicel ):

Avicel concentration of less than 10%, exhibits better disintegration. This mechanism is depending on entry of water to the tablet matrix through capillary pores, which breaks the hydrogen bonding between adjacent bundles of cellulose microcrystals. With more concentration, particularly in oral disintegrating tablet, it shows a tendency to stick to the tongue due to rapid capillary absorption and faster dehydration of the tablet surface. As Avicel has a fast wicking rate for water, hence this in combination with starch makes an excellent and rapid disintegration in OTD formulations [18-20].

5. Modified Polysaccharides:

They are biodegradable, directly compressible, having desirable swelling dynamics. The above modified polysaccharides were further used as superdisintegrants in Roxithromycin fast dispersible tablets and compared with conventional tablets containing MCC. The C-TAG and C-TGG have shown better disintegration for their porous nature, better water intake ability and free flowing property than others. Agar (AG) and guar gum (GG), natural polysaccharides are treated with water and co grinded further with mannitol which exhibit superdisintegration property. These modified polysaccharides may call C-TAG (co grinded treated agar) and C-TGG (co grinded treated guar gum) respectively [21-23].

6. Plantago ovata Seed Mucilage (Isapgula):

Isapghula consists of dried seeds of the plant Plantago ovata and it contains mucilage which is present in the epidermis of the seeds. The seeds of Plantago ovata were soaked in distilled water for 48 hrs and then boiled for few minutes for complete release of mucilage into water. The material was squeezed through muslin cloth for filtering and separating out the marc. Then, an equal volume of acetone was added to the filtrate so as to precipitate the mucilage. The separated mucilage was dried in oven at temperature less than 60°C. The mucilage of Plantago ovata is a recent innovation for its superdisintegration property when compared with Crospovidone. It shows faster disintegration time than the superdisintegrant, Crosspovidone [24-25].

7. Gellan gum:

It is an anionic polysaccharide of linear tetrasaccharides, derived from Pseudomonas elodea having good superdisintegrant property similar to the modified starch and celluloses.

8. Xanthan gum:

Xanthan Gum derived from Xanthomonas campestris is official in USP with high hydrophilicity and low gelling tendency. It has low water solubility and extensive swelling properties for faster disintegration.

9. Locust Bean gum:

Locust bean gum is extracted from the endosperm of the seeds of the carob tree Ceretoniasiliqua, which grows in Mediterranean countries. It is also called Carob bean gum. Some other familiar polysacharides are starch and cellulose, which are made of long chains of the sugar glucose. In locust bean gum, the ratio of mannose to galactose is higher than in guar gum, giving it slightly different properties, and allowing the two gums to interact synergistically so that together they make a thicker gel than either one alone. It shows as a binder and as a disintegrant property at different concentration. Pharmaceutical application of locust bean gum in various novel drug delivery systems. Locust bean gum has been widely used in food industry as a thickening and gelling agent. Locust bean gum has also been reported to have bioadhesive and solubility enhancement properties. There are various reports that Locust bean gum can be used in pharmaceutical and biotechnological purpose [26-27].

Table 2. List of Common Superdisintegrants

Sr. no	Name of excipients	Category	Conc.	Stability criteria
1	Cross-povidone	Superdisinte-grants	2-5 %	As hygroscopic in nature, stored in an air-tight container, in a cool and dry place
2	Micro-crystalline cellulose	Superdisinte-grants	5-15%	Stable at dry and air tight condition
3	Starch	Superdisinte-grants	5-10%	Stable at dry and air tight condition

CONCLUSION:

With the increase demand of novel drug delivery, the fast disintegrating drug delivery system has become one of the important tools of present investigation. The ease of availability of these agents and the simplicity in the direct compression process suggest that their use would be a more economic alternative. Rapidly disintegrating dosage forms like ODT than the sophisticated and patented techniques. have been successfully commercialized by using various kinds of superdisintegrants.

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Received on 06.04.2016 Accepted on 25.04.2016

Asian J. Res. Pharm. Sci. 2016; 6(2): 107-112

DOI: 10.5958/2231-5659.2016.00015.1

ABSTRACT: