AN OVERVIEW: ON SUPERDISINTEGRANTS

ABOUT AUTHORS:
Rahul Tiwari*¹, R.C. Jat¹, Narendra Sharma¹, Arvind Singh Rathore^1
1Shri Ram College Of Pharmacy,
¹Banmore, Morena, India -476444
*rt30022@gmail.com, arvindsingh.rathore21@gmail.com

ABSTRACT
Disintegrants are substances or mixture of substances added to the drug formulation that facilitates the breakup or disintegration of tablet or capsule content into smaller particles that dissolve more rapidly than in the absence of disintegrants. In dosage forms, solid orals gain maximum popularities, about 85%, because of many advantages over others. The therapeutic activity of these formulations is obtained through a typical manner like disintegration followed by dissolution. Hence disintegration has major role for facilitating drug activity and thus gain popularity among other dosage forms. Superdisintegrants are generally used at a low level in the solid dosage form, typically 1-  10 % by weight relative to the total weight of the dosage unit. The present study comprises the various kinds of superdisintegrants which are being used in the formulation to provide the safer, effective drug delivery with patient's compliance. In this review article, more emphasis is given on application and usage of various superdisintegrants comparing with other disintegrants in reference to available scientific studies. The various sources of superdisintegrants and their modification to improve disintegration property are also high-lighted.

REFERENCE ID: PHARMATUTOR-ART-1740

INTRODUCTION
Despite increasing interest in controlled releasedrug delivery systems, the most common tablets are those intended to be swallowed whole and to disintegrate and release their medicaments rapidly in the gastrointestinal tract (GIT) still remains the dosage form of choice^[1]. Disintegrates are substances or mixture of substances added to tablet formulations to promote the break-up 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 faster drug release. The emphasis on the availability of the drug highlights the importance of the relatively rapid disintegration of a tablet as a criterion for ensuring uninhibited drug dissolution behaviour. A number of factors affect the disintegration behaviour of tablets ^[2]. The development of fast dissolving or disintegrating tablets provides an opportunity to take into account the role of disintegrants. Recently, chemically modified disintegrants termed as superdisintegrants have been developed to improve the disintegration processes. Selection of appropriate formulation excipients and manufacturing technology can obtain the design feature of fast disintegrating tablet. 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 stronger the binder, the more effective must be the disintegrating agents in order for the tablet to release its medication. Ideally, it should cause the tablet to disrupt, not only into the granules from which it is compressed, but also into powder particles from which the granulation is prepared ^[3]. The proper choice of a disintegrant or a superdisintegrant and its consist performance are of critical importance to the formulation development of such tablets. Drug release from a solid dosage form can be enhanced by addition of suitable disintegrants. In more recent years, increasing attention has been paid to formulating not only fastdissolving and/or disintegrating tablets ^[4,5] that are swallowed, but also orally disintegrating tablets ^[6] that are intended to dissolve and/or disintegrate rapidly in the mouth. An ideal disintegrant should have poor solubility, poor gel formation, good hydration capacity, good compressibility, flow properties and no tendency to form complexes with the drugs.

SELECTION OF SUPERDISINTRIGATION:^[7,8]
Since superdisintegrant is used as an excipient in the tablet formulation, it has to meet certain criteria other than its swelling properties. The requirement placed on the tablet disintegrant should be clearly defined. The ideal disintegrant should have –
1.  Poor solubility.
2.  Poor gel formation.
3.  Good hydration capacity
4.  Good moulding and flow properties.
5.  No tendency to form complexes with the drugs.
6.  Good mouth feel.
7.  It should also be compatible with the other excipients and have desirable tableting properties.

Although some are better than others, the currently marketed superdisintegrants exhibit an optimum combination of properties

METHOD OF ADDITION OF SUPRADISINTEGRANTS
There are three methods of incorporating disintegrating agents into the tablet.

Internal Addition
In wet granulation method, the disintegrant is added to other excipients before wetting the powder with the granulating fluid. Thereby, the disintegrant is incorporated within the granules. In dry granulation method, the disintegrant is added to other excipients before compressing the powder between the rollers. In a computer optimized experiment, the study show the effect of incorporating a disintegrant, croscarmellose sodium, intragranularly, extra granularly or distributed equally between the two phases of a tablet in which a poorly soluble drug constituted at least 92.5% of the formulation. The results analyzed by means of a general quadratic response surface model suggest that, tablets with the same total concentration of crosscarmellose sodium dissolve at a faster rate when the super disintegrant is included intragranularly. Tablet friability is not affected by the method of disintegrant incorporation ^[9].

External Addition
In both wet and dry granulation method, the superdisintegrant is added to the granules during dry mixing prior to compression. The effect of mode of incorporation of superdisintegrants (croscarmellose sodium, sodium starch glycolate and crospovidone) on dissolution of three model drugs with varying aqueous solubility (carbamazepine, acetaminophen and cetrizine HCl) from their respective tablet formulations by wet granulation was studied. It is proved that crospovidone is effective in improving the dissolution of the drugs in extra granular mode of addition seems to be the best mode of incorporation, irrespective of the solubility of the main tablet component.

Internal and External Addition
In this method, disintegrant is divided into two portions. One portion is added before granule formation (intra) and remaining portion is added to granules (extra) with mixing prior to compression. This method can be more effective. If both intragranular and extragranular methods are used, extra-granular portion break the tablet into granules and the granules further disintegrate by intra-granular portion to release the drug substance into solution. However, the portion of intra-granular disintegrant (in wet granulation processes) is usually not as effective as that of extra-granular due to the fact that it is exposed to wetting and drying (as part of the granulation process) which reduces the activity of the disintegrant. Since a compaction process does not involve its exposure to wetting and drying, the intragranular disintegrant tends to retain good disintegration activity.

Mechanism of disintegrations by superdisintegrants
There are five major mechanisms for tablet disintegration as follows:-
1. Swelling
2. Porosity and Capillary Action (Wicking)
3. Deformation
4. Due to disintegrating particle/particle repulsive forces
5. Heat of wetting
6. Due to release of gases
7. Enzymatic reaction
8. Combination action

1. Swelling
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, theadhesiveness of other ingredients in a tablet is over come causing the tablet to fall apart .E.g. Sodium starch glycolate, PlatagoOvata.(fig.1)^[10,11,12]

2. Porosity and Capillary Action (Wicking)
Effective disintegrants that do not swell arebelieved 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 and 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 inter particulate bonds causing the tablet to break apart as shown in Fig 1. Crospovidones are synthetic, insoluble, crosslinked homopolymers of N-vinyl-2-pyrrolidone. Crospovidone quickly wicks saliva into the tablet to generate the volume expansion and hydrostatic pressures necessary to provide rapid disintegration. Unlike other superdisintegrants which rely principally on swelling for disintegration, crospovidones uses a combination of swelling, wicking and deformation^[13,14] formulated fast dissolving Efavirenz formulation by using three different superdisintegrants such as crosscarmellose sodium (CCS), sodium starch glycollate (SSG) and crospovidone (CP). It is concluded that CP is able to release the drug faster than the other two disintegrants.(fig.2)

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3. Deformation:  Hess  had  proved  that  during tablet compression, disintegrated particles get deformed and these  deformed  particles  get  into  their  normal  structure when  they  come  in  contact  with  aqueous  media  or  water. Occasionally,  the  swelling  capacity  of  starch  was  improved when  granules  were  extensively  deformed  during compression.(fig.3)^{[15, 16]}

4. Due to disintegrating particle/particle repulsive forces:-
Another mechanism of disintegration attempts to explain the swelling of tablet made with ‘’nonswellable’’ disintegrants. Guyot-Hermann has proposed a particle repulsion theory based on the observation that nonswelling particle 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. It is believed that no single mechanism is responsible for the action of most disintegrants. But rather, it is more likely the result of inter-relationships between these major mechanisms. (fig.4)^[17]

5. Heat of wetting:
When disintegrants with exothermicproperties get wetted, localized stress is created due to capillary air expansion, which aids in disintegration of tablet. This explanation, however, is limited to only a few types of disintegrants and cannot describe the action of most modern disintegrating agents.

6. Due  to  release  of  gases:
Carbon dioxide released within tablets on wetting due to interaction between bicarbonate and carbonate with citric acid or tartaric acid. The tablet disintegrates due to generation of pressure within the tablet. This effervescent mixture is used when pharmacist needs to formulate very rapidly dissolving tablets or fast disintegrating tablet. As these disintegrants are highly sensitive to small changes in humidity level and temperature, strict control of environment is required during manufacturing of the tablets. The effervescent blend is either added immediately prior to compression or can be added in to two separate fraction of formulation.^[18]

7. Combination action: -
In this mechanism, the combination of both wicking and swelling action facilitate disintegration. E.g. Crosspovidone

8. Enzymatic Reaction:
Enzymes present in the bodyalso act as disintegrants. These enzymes dearth the binding action of binder and helps in disintegration.Due to swelling, pressure is exerted in the outer direction that causes the tablet to burst or the accelerated absorption of water leads to an enormous increase in the volume of granules to promote disintegration. Some examples of disintegrating enzymes are presented in table 1 along with the binders against which these are active.

Table 1: some examples of enzymes as disintegranting agent

TYPES OF SUPERDISINTEGRANTS:-
The Superdisintegrants can be classified into two categories on the basis of their availability:
1  Natural Superdisintegrants.
2  Synthetic Superdisintegrants.

1.Natural  Superdisintegrants:  -These superdisinegrating agents are natural in origin and are preferred over synthetic substances because they are comparatively cheaper, abundantly available, non-irritating and nontoxic in nature. The natural materials like gums and mucilages  have been extensively used in the field of drug delivery for their easy availability, cost effectiveness, Eco friendliness, emollient and non-irritant nature, non -toxicity, capable of multitude of chemical modifications, potentially degradable and compatible due to natural origin.There are several gums and mucilages are available which have super-disintegratingavtivity.^[19]

i. Lepidiumsativum Mucilage
Lepidiumsativum (family: Cruciferae) is known as asaliyo and is widely used as  herbal medicine in India. It is widely available in market and has very low cost. Parts used are leaves, root, oil, seeds etc. Seeds contain higher amount of mucilage, dimeric imidazole alkaloids lepidine B, C, D, Eand F and two new monomeric imidazole alkaloids Semilepid inosideA and B. Mucilage of Lepidiumsativumhas various characteristic like binding,disintegrating, gelling ^[20].

ii. Plantago Ovata Seed Mucilage (Isapgula)
Isapghula consists of dried seeds of the plant plantagoovata and it contains mucilage which is present in theepidermis of the seeds. The seeds of Plantagoovatawere 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  plantagoovatais a recent innovation for its superdisintegration property when compared with Crospovidone. It shows faster disintegration time than the superdisintegrant,Crosspovidone.^[21,22]

iii. Gum Karaya
Gum Karaya is a negative colloid and a complex polysaccharide of high molecular weight. On hydrolysis it yields galactose, rhamnose and galacturonic acid. Gum Karaya occurs as a partially acetylated derivative. It is a dried exudation of sterculiaUrenstree (Family-Sterculiaceae).  Its synonyms are Karaya, sterculia, Indiantragacanth, Bassoratragacanth, kadaya, Kadira,katila. Gum Karaya is compatible with other plant hydrocolloids as well as proteins and carbohydrates.^[23,24,25]

iv.Guar gum
Guar gum is a galactomannan, commonly used in cosmetics, food products and in pharmaceutical formulations.Guar gum is mainly consisting of the high molecular weight (approximately 50,000-8,000,000) polysaccharides composed of galactomannans and is obtained from the endosperm of the seed of the guar plant, Cyamopsistetragonaloba (L) Taub. (Synonym-Cyamopsispsoraloides). It is used as thickener, stabilizer and emulsifier, and approved in most areas of the world (e.g. EU, USA,  Japan, and Australia)^[25]. Its synonyms are Galactosol; guar flour; jaguar gum; meprogat; meyprodor.  It has also been investigated in the preparation of sustained release matrix tablets in the place of cellulose derivatives such as methylcellulose. In pharmaceuticals, guar gum is used in solid-dosage forms as a binder and disintegrant, and in oral and topical products as a suspending, thickening, and stabilizing agent, and also as a controlled-release carrier. Guar gum has also been examined for use in colonic drug delivery .^{[26, 27]}

v. Fanugreek Seed Mucilage
Trigonella Foenum-graceum, commonly known as Fenugreek, is an herbaceous plant of the leguminous family. It has found wide applications as a food, a food additive, and as a traditional medicine. The leaves and both   the ripe and unripe seeds of Trigonella Foenum-graceumare used as vegetables. Fenugreek has been used in treating colic flatulence, dysentery, diarrhoea, dyspepsia with loss of appetite, chronic cough, dropsy, enlargement of liver and spleen, rickets, gout, and diabetes. It is also used as gastro protective, antiurolithiatic, diuretic, antidandruff agent, Anti-inflammatory agent and as antioxidant. The seed is stated to be a tonic.  It also is used in post-natal care and to increase lactation in nursing  mothers. Fenugreek seeds contain a high percentage of mucilage (a natural gummy substance present in the coatings of many seeds). Although it does not dissolve in water, mucilage forms a viscous tacky mass when exposed to fluids. Like other mucilage-containing substances, fenugreek seeds swell up and become slick when they are exposed to fluids. The resulting soft mass is not absorbed by the body, but instead passes through the intestines and triggers intestinal muscle contractions.^[28,29]

vi. 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.^[30,31]

2. Synthetic Superdisintegrants
A group of superdisintegrants including croscamellose sodium (Ac-Di-Sol) sodium starch glycolate (Primojeland Explotab) and crospovidone (Polyplasdone XL) alleviate most of these problems. Use of the superdisintegrants in fast dispersible tablet is possible as tablet shows optimum physical properties.^[32]

Advantages of Synthetic Superdisintegrants

·         Effective in lower concentrations than starch.

·         Less effect on compressibility and flow ability.

·         More effective intragranularly.^[33]

i. Sodium Starch Glycolate:(Explotab, Primogel)
Sodium starch glycolate is widely used in oral pharmaceuticals as a disintegrant in capsule and tablet formulations. It is recommended to use in tablets prepared by either direct-compression or wet-granulation processes. The recommended concentration in a formulation is 2-8%, with the optimum concentration about 4% although in many cases 2% is sufficient.  Disintegration occurs by rapid uptake of water followed by rapid and enormous swelling. Thedisintegrant efficiency of sodium starch glycolate is unimpaired in the presence of hydrophobic excipients, such as lubricants unlike many other disintegrants. Increasing the tablet compression pressure also appears to have no effect on disintegration time. These are modified starches with dramatic disintegrating properties and are available as explotab and primogel which are low substituted carboxy methyl starches. Explotab consisting of granules that absorb water rapidly and swell. The mechanism by which this action takes place involves rapid absorption of water leading to an enormous increase in volume of granules result in rapid and uniform disintegration. The natural predried starches swell in water to the extent of 10-20 percent and the modified starches increase in volume by 200-300 percent in water. ^[34,35]

ii. Cross-linked polyvinyl-pyrrolidone:
(crospovidone,PolyplasdoneXL,XL10) 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, Crospovidone superdisintegrants use a combination of swelling and wicking. When examined under a scanning electron microscope, crospovidone particles appear granular and highly porous.

This unique, porous particle morphology facilitates wicking of liquid into the tablet and particles to generate rapid disintegration. Due to its high crosslink density, crospovidone swells rapidly in water without gelling. Other superdisintegrants have a lower crosslink density and, as a result, form gels when fully hydrated, particularly at the higher use levels in ODT formulations. Swells very little and returns to original size after compression but act by capillary action^[36,37,38].

iii. Cellulose Derivatives (Ac-Di-Sol®)
Croscarmellose sodium is described as a cross-linked polymer of carboxy methyl  cellulose (CMC). This polymer is different in synthesis and structure as compare to Sodium starch glycolate. Most importantly, the degree of substitution using Williamson’s ether synthesis of croscarmellose sodium is higher than that of sodium starch glycolate, and the mechanism of crosslinking is also different. The chemistry of SSG is different that of cross carmellose sodiumAs  some of the carboxymethyl groups themselves are used to cross-link the cellulose chains. For example, the cross-linking in Primogel are phosphate ester rather than carboxyl ester links as compare to Cross carmellose sodium.

iv. Alginates
These are hydrophilic colloidal substances extracted naturally from certain species of Kelp or chemically modified from natural sources like alginic acid or salt of alginic acid. They are having higher affinity for water absorption and capable for an excellent disintegrants. They can be successfully used with ascorbic acid, multivitamins formulation.

v. Chitin/Chitosan–Silicon Dioxide Coprecipitate
Chitin is one of the recent and most interesting category of superdintegrant. It is the second most abundant polysaccharide found in nature after cellulose Naturally Chitin is extracted from the shell wastes of shrimp, crab, lobster, krill, and squid and used for the production of chitosan by a deacetylation reaction in alkaline medium. However, in large-scale handling of pharmaceutical blends both chitin and chitosan  n powders show poor bulk density, thus results in poor flowability and compressibility.^[39]

The comparative study of other superdisintegrants with chitin–silica coprecipitate has proved better disintegration and dissolution functionality. The  particle rearrangement and plastic deformation ability of chitin–silica undergoes in the same extent compared with Avicel. The good compressibility and the good compactability properties of chitin–silica may allow it to be used in direct compression applications.^[40,41]

vi . Ion Exchange Resins
The INDION 414 has been used as a superdisintegrant for ODT. It is chemically cross-linked polyacrylic, with a functional group of – COO – and the standard ionic form is K+ and is a weak acid cationic exchange resin. It has a high water uptake capacity. It is a high purity pharmaceutical grade weak acid cation exchange resin supplied as a dry powder. It is an extremely effective superdisintegrant which provides the necessary hardness and chemical stability to the tablet. The product swells up to a very great extend when in contact with water or gastrointestinal fluids causing rapid disintegration without the formation of lumps. It is a high molecular weight polymer, therefore it is not absorbed by the human tissues and totally safe for human consumption.

vii. Modified Polysaccharides
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.^[42,43]

They are biodegradable, directly compressible, having desirable swelling dynamics. The above modified polyschharides 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. Another natural polysscharide, karaya gum is modified using distilled water to achieve superdisintegration property in dispersible tablet development. This modified karaya gum (MKG) is easy to prepare, cheap, easily available, biodegradable and stable compared to available synthetic super disintegrants in market.

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Applications of superdisintegrants
The uses of superdisintegrants are  extended in the applications of oral disintegration tablets, fast-dispersible tablets, capsules, mouth-dissolving films,  etc. Particularly for ODTs and fast dispersible tablets, are optimized based on their disintegration time. ODTs need to be disintegrated in the presence of saliva in oral cavity within a minute. Thus these formulations achieve better patient compliance in  all classes from pediatric to geriatric, bedridden and uncooperative patients including frequent travelers as it requires little or no access of water.^[44]

Few marketed formulations containing superdisintegrant(s) are high-lighted in the table no.2.

Table 2. Marketed Orally disintegrating formulations

This review article inclined towards the approach of superdisintegrants in various formulations, the innovations, already patented in related field are listed as

1. Pharmaceutical superdisintegrant  (US20050100600): Superdisintegrants which provide improved compressibility compared to prior art superdisintegrants. The superdisintegrants include a particulate agglomerate of coprocessed starch or cellulose and a sufficient amount of an augmenting agent to increase the compactibility of the superdisintegrant.

2. Rapidly disintegrating enzyme-containing solid oral dosage compositions  (US20060013807):  Invention relates to rapidly disintegrating solid oral dosage forms having an effective amount of an enzyme and a superdisintegrant. The enzyme lactase is claimed in this patent for solid oral formulations.

3.  Fast disintegrating tablets  (US20050169986):  A fast disintegrating tablet comprising Nimesulide and one or more disintegrants. In this research superdisintegrants used are croscarmellose cellulose, crospovidone and sodium starch glycolate.

4.  Method of producing fast dissolving tablets (US20100074948):  A method of producing a fast-melt tablet. The process does not involve any granulation step, thereby making the process more energy efficient and cost effective. The fast dissolving sugar alcohol is selected from the group comprising: mannitol; sorbitol; erythritol; xylitol; lactose; dextrose; and sucrose. The active component is suitably provided in the form of microparticles or microcapsules having an average diameter of less than 125 microns.

5. Disintegrating Loadable Tablets  (US20090186081):  A disintegrating loadable tablet product in compressed form. A disintegrant or a mixture of disintegrants has a) porosity of 45% v/v or more, b) a hardness of at least 20 Newton, and c) a loading capacity of at least 30% of a liquid.

6. Rapidly disintegrating tablet (US20060115528): The study relates to rapidly disintegrating tablets intended to be used as orodispersible tablets or dispersible tablets. The tablets include silicified microsrystalline cellulose. They are especially suitable for antibiotics. Rapidly disintegrating tablets which contain amoxicillin and clavulanic acid are also described.

CONCLUSION:
With  the  increase  demand  of  novel  drug  delivery,  the  fast disintegrating  drug  delivery  system  has  become  one  of  the mile  stone  of  present  investigation. The innovations in the arena of formulating ODTs are aimed at both increasing the performance of the dosage form by decreasing the disintegration time .This article attempted to unveil the strategies that have been used by inventors for improving the performance of Superdisintegrants. The use of Superdisintegrants for achieving these aims is not new. However, with the improvement innovation of superdisintegrating agents it has become possible to develop ODTs with reduced content of superdisintegrants. Similarly, considerable research towards producing modified microcrystalline cellulose or starch in order to engineer them suitable for direct compression has significantly reduced the product development time for optimizing ODT formulation. Rapidly disintegrating dosage forms have been successfully commercialized by using various kinds of superdisintegrants.

REFRENCES:
1. Rao V.U., Preetha B., Pandit J.K., Bindu K., Rajesh Y.V., and Balasubramaniam J.Comparative evaluation of mode of incorporation of superdisintegrants on dissolution of model drugs from wet granulated tablets. Acta Pharmaceutica Sciencia. 2008;50: 229-236.
2. Mohanachandran P.S., Sindhumol P.G, Kiran T.S. Superdisintegrants: an overview. International Journal of Pharmaceutical Sciences Review and Research.2011, 6(1):105-109.
3. Sampath Kumar K. P., Debjit Bhowmik, Chiranjib. B, Jitendra Yadav, Chandira R. M. Emerging trends of disintegrants used in formulation of solid dosage form. Der Pharmacia Lettre, 2010;2 (1) 495-504.
4. Bi Y. X., Sunada H., Yonezawa Y., and Danjo K. Evaluation of rapidly disintegrating tablets prepared by a direct compression method. Drug Dev Ind Pharm. 1999; 25(5):571-581.
5. Sallam E., Ibrahim H., Abu Dahab R., Shubair M. and Enam Khali Evaluation of fast disintegrants in terfenadine tablets containing a gas-evolving disintegrant. Drug Dev Ind Pharm. 1998;24(6):501-507.
6. Bi Y, Sunada H, Yonezawa Y, Danjo K,Otsuka A, Iida K. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. chem pharm bull (tokyo). 1996; 44(11):2121-2127.
7. Omidian H and Park K: Swelling agents and devices in oral drug delivery. Journal of Drug Delivery Science and Technology 2008; 18 (2): 83-93.
8. Iyad R, Mayyas AR, Eftaiha AA and Badwan A: Chitin-silicon dioxide coprecipitate as a novel superdisintegrant. Journal of Pharmaceutical Sciences 2008; 97(11): 4955-69
9. Marc S. Gordon, Bikash Chatterjee, Zak T.Chowhan. Effect of the mode of croscarmellose sodium incorporation on tablet dissolution and friability. Journal of Pharmaceutical Sciences. 1990;79(1): 43–47.
10. D.chougule, ghodke.dhananjay, r. rshah&rahulghaste. Fast Dissolving Tablets: An Overview. (2010)
11. formulationvinensia.com
12. N. G. R. Rao, T. Ketan& S. Bala. Formulation and evaluation of fast dissolving Tablets of Metoprolol Tartrate using Natural superdisintegrant. International Journal of Pharmaceutical and Clinical Research. 2 (2010) 40-45.
13. Solution for poorly soluble drugs www.isppharmaceuticals.com.
14. Rajesh YV, Balasubramaniam J, Bindu K, Sridevi R, Swetha M, Rao V U. Impact of superdisintegrants onefavirenz release from tablet formulations. Acta Pharm. 2010;60 (2):185-95.
15. Kuchekar BS, Bhise SB and Arungam V. Design of Fast Dissolving Tablets. Indian J Pharm Edu 2005; 35:150.
16. Reddy LH, Ghosh B and Rajneesh. Fast dissolving drug delivery system: A review of literature. Indian J Pharm Sci 2002; 64(4):331336.
17. V. D. kumar, I. Sharma & V. Sharma. A comprehensive review on fast dissolving tablet technology. Journal of Applied Pharmaceutical Science. 01 (05); (2011) 50-58.
18. Kuchekar BS, Bhise SB and Arungam V. Design of Fast Dissolving Tablets. Indian J Pharm Edu 2005; 35:150
19. M.P.Khinchi, M.K.Gupta, A.Bhandari, D.Agarwal & N.Sharma. Studies on the Disintegrant Properties Of Seed Powder, Husk Powder And Mucilage Of PlantagoOvata By Formulation Of Orally Disintegrating Tablet. International Journal of Pharmaceutical Sciences and Research. Vol.2 (2011) 145-152
20. K. K. Mehta, H. H. Patel, N. D. Patel, C. N. Vora& N. J.Patel. Comparative Evaluation of Natural And Synthetic Superdisintegrant For Promoting Nimesulide Dissolution For Fast Dissolving Technology. International Journal Of Pharmacy And Pharmaceutical Sciences.1 (2010) 102-108.
21. R.Deveswaran, S.Bharath, S. Furtado, B.V.Basavaraj, S. Abraham &V.Madhavan. Studies on the Disintegrant properties of Mucilage and Seed Powder of Plantagoovata. International Journal of ChemTech Research. 1 (2009) 621-626.
22. S. Shirsand, S. Suresh, M. Para, P. Swamy& D. N. Kumar. Plantagoovata mucilage in the design of fast disintegrating tablets. Indian Journal OfPhrmaceutical Science. 71 (2009) 41-45.
23. N. Bansal& G. Sharma. Formulation and Evaluation of Orally Disintegrating Tablets Of Ondansetron Hydrochloride Using Natural Superdisintegrants. International Journal Of Pharmatech Research, IJPRIF (2011) 1616-1621.
24. C.K. Kokate, PurohitAP,Gokhle SB, Pharmacognosy , Thirteen ed., NiraliPrakashan, New Delhi, 2005.
25. www.willy-benecke.com/karaya_f.html; www.drugs.com/npp/karaya-gum.html.
26. Liberman, H. A., L. Lachman and J. B. Schawstr., Pharmaceutical Dosage Forms: Tablets. Vol.2. 1989.
27. R.J.Chudzikowski. Guar gum and its Application. J SocCosmt Chem. 22 (1971) 43-60.
28. R. Malviya, P. Srivastava& G. T. Kulkarni. Applications of Mucilages in Drug Delivery A Review. Advances in Biological Research. 5 (2011) 1-7.
29. R. Kumar, S. Patil, M. B. Patil, S. R. Patil& M. S. Paschapur. Isolation and Evaluation of Disintegrant Properties of Fenugreek Seed Mucilage. International Journal ofPharmTech Research, IJPRIF.1 (2009) 982-996.
30. P. Dey, S. Maiti& B. Sa. Locust Bean Gum and Its Application in Pharmacy And Biotechnology: An Overview. International Journal of Current Pharmaceutical Research. 4 (2011) 7-11.
31. K. Malik, G. Arora& I. Singh. Locust bean Gum as Superdisintegrant – Formulation and Evaluation of NimesulideOrodispersible Tablets. Polimery w Medycynie (2011) 18-28.
32. S. Bhise, G.Chaulang, P. Patel, B. patel, A. Bhosale& S. Hardikar. Superdisintegrants as solubilizing agent. Research J. Pharm. and Tech. 2(2) (2009) 387-391
33. R. Bala, S. Khanna& P. Pawar. Polymers In Fast Disintegrating Tablet A Review. Asian Journal of Pharmaceutical and Clinical Research, 5 (2012) 8-14.
34. Liberman, H. A., L. Lachman and J. B. Schawstr., Pharmaceutical Dosage Forms: Tablets. Vol.2. 1989
35. S. Selvi, B. S., R. R, Y.Chandrasekhar& P. Perumal. Orodispersible Tablets Of Lornoxicam with Natural and Synthetic Super Disintegrants. International Journal of Pharmacy And Technology. 3 (2011) 3130-3142.
36. R. S. Kiran, P. Vishnu, B. Ravendrababu, B. Sudeerbabu, K. Naveenbabu& M. Prasad. Influence of various super disintegrating agents on the aceclofenac fast dissolving tablets. Research Journal of Pharmaceutical, Biological and Chemical Sciences, 2 (2011) 99-105.
37. A. Fini, V. Bergamante, G. C. Ceschel, C. Ronchi& C. A. F. d. Moraes. Fast dispersible/slow releasing ibuprofen tablets. European Journal of Pharmaceutics and Biopharmaceutics. 69 (2007) 335-341
38. J. Fukami, E. Yonemochi, Y. Yoshihashi& K. Terada. Evaluation of rapidly disintegrating tablets containing glycine and carboxymethylcellulose. International Journal of Pharmaceutics. 310 (2006) 101-109.
39. Soares LL, Ortega GG, Petrovick PR, Schmidt PC. 2005. Optimization of tablets containing a high dose of spray-dried plant extract: A technical note. AAPS PharmSciTech 06:E367–E371.
40. Watanable Y, et al. 2001. Preparation of rapidly disintegrating tablets using new type of MCC (PHM- Series) and L-HPC by direct compression method. Chemical & pharmaceutical Bulletin 49:134–139.
41. Chen CR, Lin YH, Cho SL, Yen SY, Wu HL. 1997. Investigation of the dissolution difference between acidic and neutral media of acetaminophen tablets containing a super disintegrant and a soluble excipient. Chem Pharm Bull 45:509–512.
42. Satoskar R S, Bhandarkar S D, and Rege N N Pharmacology and Pharmacotherapeutics, 19th ed., Popular Prakashan Pvt.Ltd, Mumbai, India, 2005, p.665.
43. Joshifusa S, Suzuki H, Hironaka K, and Kunio I. Studies of rapidly disintegrating tablets in the oral cavity using co-ground mixtures of mannitol with crosspovidone. Chemical & Pharmaceutical Bulletin, 50(2):193–198 (2002).
44. Basawaraj S P, Kulkarni U, Beknal A K, Srinivas R S, Formulation and Evaluation of Fast Dissolving Tablets of Tizanidine Hydrochloride by Direct Compression Method, JPSBR, 2011; 1(1); 71-77

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