You are on page 1of 22

1.0.

INTRODUCTION

Oral delivery is currently the gold standard in the pharmaceutical industry as it offers advantages like ease of administration, versatility, patient compliance and accurate dosing. Patient compliance, high-precision dosing, and manufacturing efficiency make tablets the solid dosage form of choice. Undesirable taste is one of the important formulation problems that are encountered with such oral products. Difficulty in swallowing is also a common problem of all age groups, especially the elderly and pediatrics, because of physiological changes associated with these groups. Many patients have difficulty in swallowing tablets and hard gelatin capsules and consequently they may not take medications as prescribed.Other categories that experience problems using conventional oral dosage forms includes the nauseated, mentally ill, and non cooperative patients, those with motion sickness, sudden episodes of allergic or asthma attack where an ultra-rapid onset of action is required. (Kanakadurga DN et al., 2010) For this reason innovative drug delivery systems known as fast dissolving tablets have developed.The concept of fast dissolving drug delivery system emerged from the desire to provide patient with more conventional means of taking their medication and avoids missing out of dose even during travelling busy or other situations where there is no access to water. They undergo disaggregation in the mouth when in contact with the saliva within two minutes, preferably in less than 40seconds, forming a suspension which is easy to swallow. The potential advantages of such tablets include, administration without water, anywhere, anytime lead to their suitability to geriatric, pediatric, mentally ill, the bedridden and patients who do not have easy access to water. The benefits, include accurate dosing as compare to liquids, easy portability, ability to provide advantages of liquid medication in the form of solid preparation, rapid dissolution or absorption of the drug, which may produce rapid onset of action, increased bioavailability, and good stability make these tablets popular as a dosage form of choice in the current market.( Biraju patel et al., 2009)

1.1. Solubility Introduction Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. It is defined as the phenomenon of dissolution of solute in solvent to give a homogenous system. It is one of the important parameters to achieve desired concentration of drug in systemic circulation for desired pharmacological response. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. (Ketan T. Savjani et al., 2012) 1.1.1. Importance of Solubility Oral ingestion is the most convenient and commonly employed route of drug delivery due to its ease of administration, high patient compliance, cost effectiveness, least sterility constraints, and flexibility in the design of dosage form. The major challenge with the design of oral dosage forms lies with their poor bioavailability. The oral bioavailability depends on several factors including aqueous solubility, drug permeability, dissolution rate, first-pass metabolism, pre systemic metabolism, and susceptibility to efflux mechanisms. The most frequent causes of low oral bioavailability are attributed to poor solubility and low permeability. Solubility is one of the important parameters to achieve desired concentration of drug in systemic circulation for achieving required pharmacological response (V. R. Vemula et al., 2010). Poorly water soluble drugs often require high doses in order to reach therapeutic plasma concentrations after oral administration. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as generic development. Any drug to be absorbed must be present in the form of an aqueous solution at the site of absorption. Water is the solvent of choice for liquid pharmaceutical formulations. Most of the drugs are either weakly acidic or weakly basic having poor aqueous solubility. More than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically insoluble in water. These poorly water soluble drugs having slow drug absorption leads to inadequate and variable bioavailability and gastrointestinal mucosal toxicity. For orally administered drugs solubility is the most important rate limiting parameter to achieve their desired concentration in systemic
2

circulation for pharmacological response. The improvement of drug solubility thereby its oral bioavailability remains one of the most challenging aspects of drug development process especially for oral-drug delivery system. The poor solubility and low dissolution rate of poorly water soluble drugs in the aqueous gastrointestinal fluids often cause insufficient bioavailability. Especially for class II (low solubility and high permeability) substances according to the BCS, the bioavailability may be enhanced by increasing the solubility and dissolution rate of the drug in the gastrointestinal fluids. As for BCS class II drugs rate limiting step is drug release from the dosage form and solubility in the gastric fluid and not the absorption, so increasing the solubility in turn increases the bioavailability for BCS class II drugs (A. Kumar et al., 2010). There are numerous approaches available and reported in literature to enhance the solubility of poorly watersoluble drugs. Various techniques are used for the enhancement of the solubility of poorly soluble drugs which include physical and chemical modifications of drug and other methods like particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, complexation, and so forth. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics. The techniques are chosen on the basis of certain aspects such as properties of drug under consideration, nature of excipients to be selected, and nature of intended dosage form. (Ketan T. Savjani et al., 2012) 1.2. Solid dispersions Solid dispersion (SD) is dened as the dispersion of one or more active ingredients in inert carriers at solid state prepared by fusion, solvent, or solvent-fusion methods. It has been widely used to improve the dissolution rate, solubility and oral absorption of poorly water-soluble drugs. In solid dispersions, the particle size of the drugs was reduced, the wettability and the dispersibility were enhanced; therefore, drug dissolution was improved markedly. (Mahmoud El-Badry et al., 2009) 1.2.1. Advantages of Solid Dispresion Preparation of solid dispersions results in particles with reduced particle size and thus surface area is improved and increased dissolution rate is attained. The ultimate result is improved bioavailability.

Wettability is improved during solid dispersion production. Improved wettability results in increased solubility. The carriers play the major role to improve the wettability of the particles. Particles in solid dispersions have been found to have a higher degree of porosity. The increased porosity of solid dispersion particles accelerates the drug release profile. Increased porosity also depends on the carrier properties. In solid dispersions drugs are presented as supersaturated solutions which are considered to be metastable polymorphic form. Thus presenting drugs in amorphous form increase the solubility of the particles. Rapid dissolution rates that result in an increase in the rate and extent of the absorption of the drug, and a reduction in presystemic metabolism, hence both can lead to the need for lower doses of the drug. (Dixit AK et al., 2012) 1.2.2. Disadvantages of solid dispersion systems Limitations of this technology have been a drawback for the commercialization of solid dispersions. The limitations include: Laborious and expensive methods of preparation, Reproducibility of physicochemical characteristics, Difficulty in incorporating into formulation of dosage forms, Scale-up of manufacturing process, and Stability of the drug and vehicle. Method of preparation (Ruchi Tiwari1 et al., 2009) 1.2.3. Methods Of Preparation Of Solid Dispersions Fusion method solvent evaporation method Melting solvent method Melt extrusion method Lyophilisation Technique Melt Agglomeration Process Use of surfactant Electrospinning Super Critical Fluid (Scf) Technology
4

Figure 1: Methods of preparation of Solid Dispersion (Ruchi Tiwari1 et al., 2009) Fusion /Melting Method The melting or fusion method, first proposed by Sekiguchi and Obi involves the preparation of physical mixture of a drug and a water-soluble carrier and heating it directly until it melted. The melted mixture is then solidified rapidly in an icebath under vigorous stirring. The final solid mass is crushed, pulverized and sieved. However many substances, either drugs or carriers, may decompose or evaporates during the fusion process which employs high temperature. Some of the means to overcome these problems could be heating the physical mixture in a sealed container or melting it under vacuum or in presence of inert gas like nitrogen to prevent oxidative degradation of drug or carrier.

Advantages The main advantage of direct melting method is its simplicity and economy. In addition melting under vacuum or blanket of an inert gas such as nitrogen may be employed to prevent oxidation of drug or carrier. Disadvantages Major disadvantage is that the method can only be applied when drug and matrix are compatible and when they mix well at the heating temperature. (Dixit AK et al., 2012) Solvent Evaporation Method The solvent-based process uses organic solvent to dissolve and intimately disperse the drug and carrier molecule. Identification of a common solvent for both drug and carrier can be problematic, and complete solvent removal from the product can be a lengthy process. Moreover suitable alterations in the concentrations used for solvent evaporation may lead to large changes in the product performance. In addition large volumes of Solvents are generally required which can give rise to toxicological problems12, 50. Many investigators studied solid dispersions of Meloxicam16, Naproxen58, 64, Rofecoxib78, Felodipine50, Atenolol55, and Nimesulide40 using solvent evaporation techniques. These findings suggest that the above-mentioned technique can be employed successfully for improvement and stability of solid dispersions of poor water drugs. Bhanbhun M Suhagic suggested a method for preparation of solid dispersions of etoricoxib employing solvent evaporation process wherein carrier is poly ethyl glycol (PEG) and PVP along with drug were dissolved in 2-propanol to get a clear solution and solvent was evaporated79. The prepared solid dispersions exhibited improved dissolution attributed to decreased crystallinity, improved wetting and improved bioavailability.
(V. Kamalakkannan et al., 2010)

Hydrophobic crystalline drug

Hydrophilic carrier

Dissolve in organic solvent Remove the solvent by vaccum Solid dispersion (molecular dispersed or amorphous drug in hydrophilic carrier matrix)

Figure 2: A schematic representation of preparation of solid dispersion by solvent evaporation technique (V. Kamalakkannan et al., 2010) Disadvantages The higher cost of preparation. The difficulty in completely removing liquid solvent. The possible adverse effect of traces of the solvent on the chemical stability The selection of a common volatile solvent. The difficulty of reproducing crystal form. In addition, a super saturation of the solute in the solid system cannot be attained except in a system showing highly viscous properties. (Serajuddin A et al., 1999) 1.3. Fast dissolving tablets Fast disintegrating tablets are dosage forms, which disintegrate in patients mouth within a few seconds without the need of water, or chewing, providing best remedy for the patient suffering from dysphasia(Gedam Shweta S et al., 2010). The bioavailability of some drugs may be increased due to absorption of drug in oral cavity and also due to pregastric absorption of saliva containing dispersed drugs that pass down into the stomach.The amount of drug that is subjected to first pass metabolism is reduced as compared to standard tablet (Debjit Bhowmik et al., 2009). The potential advantages of such tablets include, administration without water, anywhere, anytime lead to their
7

suitability to geriatric, pediatric, mentally ill, the bedridden and patients who do not have easy access to water. The benefit of such formulations includes patient compliance, rapid onset of action and increased extent of bioavailability. Fast disintegrating drug delivery systems have started gaining popularity and acceptance as new drug delivery systems which aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance (Gandhi1 CK et al., 2011). 1.3.1. Ideal properties of Orally Disintegrating Tablets ODTs should depict some ideal characteristics to distinguish them from traditional conventional dosage forms. Important desirable characteristics of these dosage forms include: No water requirement for swallowing purpose but it should dissolve or disintegrate in the mouth usually within fraction of seconds. Provide pleasant feeling in the mouth. Be compatible with taste masking. Be portable without fragility concern. Leave negligible or no residue in the mouth after oral administration. Exhibit low sensitivity to altered environmental conditions such as humidity and temperature. Allow high drug loading. Adaptable and amenable to conventional processing and packaging equipment at nominal expense. ( Rakesh Pahwa et al., 2010) 1.3.2. Advantages of Oral Disintegrating Tablets Oral Disintegrating Tablets offer dual advantages of solid dosage forms and liquid dosage forms along with special features which include: Accurate dosing Being unit solid dosage forms, provide luxury of accurate dosing, easy Portability and manufacturing, good physical and chemical stability and an ideal alternative for pediatric and geriatric patients.

Enhanced bioavailability Bioavailability of drugs is enhanced due to absorption from mouth, pharynx and esophagus. Rapid action Fast onset of therapeutic action as tablet gets disintegrated rapidly along with quick dissolution and absorption in oral cavity. Patient compliance No need of water to swallow the dosage form. Hence, it is convenient for patients who are traveling and do not have immediate access to water. Ease of administration Convenient to administer specially for geriatric, pediatric, mentally disabled and bed ridden patients who have difficulty in swallowing. Obstruction free No risk of suffocation in airways due to physical obstruction when swallowed, thus providing improved safety and compliance. Enhanced palatability Good mouth feel, especially for pediatric patients as taste masking technique is used to avoid the bitter taste of drug. Simple packaging No specific packaging required. It can be packaged in push through blisters. Business avenue Provide new business opportunities in the form of product differentiation, line extension, uniqueness and life cycle management. Cost effective Conventional processing and packaging equipments allow the manufacturing of tablets at low cost.( Rakesh Pahwa et al., 2010) 1.3.3. Disadvantages mouth dissolving tablets Careful handling is required because tablets usually have insufficient mechanical strength.

If tablets are not formulated properly they may leave unpleasant taste or grittiness in the mouth. Drugs difficult to formulate into FDT with relatively larger doses. Drugs with short half-life and frequent dosing and those whom require controlled or sustained release are unsuitable candidates of FDTs. RDT requires special packaging for properly stabilization & safety of stable product. (Patidar ashish et al., 2011) 1.3.4. Selection of drug candidates for ODTs Several factors must be considered while selecting an appropriate drug candidate fordevelopment of orally disintegrating dosage forms. The ultimate characteristics of a drug for dissolution in the mouth and pregastric absorption from ODTs include: Free from bitter taste. Dose lower than 20 mg. Small to moderate molecular weight. Good solubility in water and saliva. Partially nonionized at the oral cavity's pH. Ability to diffuse and partition into the epithelium of the upper GIT (log P >1, or preferably >2). Ability to permeate oral mucosal tissue. (Priyanka Nagar et al., 2011) 1.3.5. Pharmacological class of drugs suitable to formulate as fast dissolving tablets There are no particular limitations as long as it is a substance which is used as a pharmaceutical active ingredient. Researchers have formulated ODT for various categories of drugs used for therapy in which rapid peak plasma concentration is required to achieve the desired pharmacological response. These include neuroleptics, cardiovascular agents, analgesics,antiallergic, anti-epileptics, anxiolytics, sedatives, hypnotics,diuretics, anti-parkinsonism agents, anti-bacterial agents and drugs used for erectile dysfunction. (Kushekar et al., 2003)
10

1.3.6. Conventional Techniques Used in the Preparation of Fast Dissolving Drug Delivery Systems Various technologies used in the manufacture of Fast dissolving tablets include Freeze drying or lyophilization Tablet Molding Direct compression Spray drying Sublimation Mass extrusion Cotton Candy process Melt Granulation Phase Transition Nanonization Fast Dissolving Films Freeze-Drying or Lyophilization Freeze drying is the process in which water is sublimed from the product after it is frozen. Lyophilisation is a pharmaceutical technology which allows drying of heat sensitive drugs and biologicals at low temperature under conditions that allow removal of water by sublimation. This technique creates an amorphous porous structure that can dissolve rapidly. Lyophilisation results in preparations, which are highly porous, with a very high specific surface area, and which dissolve rapidly and show improved absorption and bioavailability.The active drug is dissolved or dispersed in an aqueous solution of a carrier/polymer. The mixture is done by weight and poured in the walls of the preformed blister packs. The trays holding the blister packs are passed through liquid nitrogen freezing tunnel to freeze the drug solution or dispersion. Then the frozen blister packs are placed in refrigerated cabinets to continue the freeze-drying. After freezedrying the aluminum foil backing is applied on a blister-sealing machine. Finally the blisters are packaged and shipped. (Debjit Bhowmik et al., 2009)

11

Advantages of Freeze drying Tablets produced by this technique possess very low disintegration time. Render tablets with great mouth feel due to fast melting effect. Provides immediate dissolution (5 sec). Increases absorption and bioavailability of drug. Lyophilization is useful for heat a sensitive drug that is thermo labile substances. Tablets prepared by lyophilization disintegration rapidly in less than 5 sec due to quick penetration of saliva in pores when placed in oral cavity. Disadvantages of freeze drying Relatively expensive and time consuming process. The product obtained is poorly stable and fragile, sensitive to humidity rendering conventional packaging unsuitable. Very poor physical resistance. High cost of production. Low dose of water-soluble drugs. (Priyanka Nagar et al., 2011) Tablet Molding Molding process is of two types i.e. solvent method and heat method. Solvent method involves moistening the powder blend with a hydro alcoholic solvent followed by compression at low pressures in molded plates to form a wetted mass. The solvent is then removed by air-drying. The tablets manufactured in this manner are less compact than compressed tablets and posses a porous structure that hastens dissolution. The heat molding process involves preparation of a suspension that contains a drug, agar and sugar (e.g. mannitol or lactose) and pouring the suspension in the blister packaging wells, solidifying the agar at the room temperature to form a jelly and drying at 300C under vacuum. The mechanical strength of molded tablets is a matter of great concern. Binding agents, which increase the mechanical strength of the tablets, need to be incorporated. Taste masking is an added problem to this technology. The taste masked drug particles were prepared by spray congealing a molten mixture of hydrogenated cottonseed oil,
12

sodium carbonate, lecithin, polyethylene glycol and an active ingredient into a lactose based tablet triturate form. Compared to the lyophillization technique, tablets produced by the molding technique are easier to scale up for industrial manufacture. (Ashok Kumar et al., 2011) Direct compression Direct compression is one of the popular techniques for preparation of these dosage forms. The advantages of this method include easy implementation, use of conventional equipments along with commonly available excipients, limited number of processing steps and cost effectiveness. Disintegration and solubilization of directly compressed tablets depend on single or combined action of disintegrants, water-soluble excipients and effervescent agents. The basic principle involved in development of these dosage forms using this technique is addition of superdisintegrants in optimum concentrations so as to achieve rapid disintegration along with pleasant mouth feel. It is considered as the best method to prepare orally disintegrating dosage forms since the prepared tablets offer higher disintegration due to absence of binder and low moisture contents. This approach is also considered as disintegrant addition technology. (Rakesh Pahwa et al., 2010) Advantages Requires fewer unit operations compared with wet Granulation (shorter processing time and lower energy consumption) Fewer stability issues for actives that are sensitive to heat or moisture For certain compounds, faster dissolution rates may be generated from tablets prepared by direct compression compared with wet granulation; for example, Norfloxacin. Fewer excipients may be needed in a direct compression Formula. `Disadvantages Issues with segregation these can be reduced by matching The particle size and density of the active drug substance with excipients
13

In general, the drug content is limited to approximately 30% or approximately 50 mg Not suited for poorly flowing drug compounds Static charges may develop on the drug particles or excipients during mixing, which may lead to agglomeration of particles producing poor mixing. (Priyanka
Nagar et al., 2011)

Spray drying In this technique gelatin can be used as a supporting agent and as a matrix mannitol as a bulking agent and sodium starch glycolate or crosscarmellose or crospovidone are used as superdisintegrants. Tablets manufactured from the spray-dried powder have been reported to disintegrate in less than 20 seconds in aqueous medium. The formulation contained bulking agent like mannitol and lactose, a superdisintegrant like sodium starch glycolate & croscarmellose sodium and acidic ingredient (citric acid) and/or alkaline ingredients (e.g. sodium bicarbonate). This spray-dried powder, which compressed into tablets showed rapid disintegration and enhanced dissolution. (Debjit Bhowmik et al., 2009) Sublimation
This technique is based on the use of volatile ingredients (e.g. camphor, ammonium bicarbonate, naphthalene, urea, urethane etc.) to other tablet excipients and the mixture is then compressed into tablets. Entrapped volatile material is then removed via sublimation, which leads to formation of a porous structure. These compressed tablets which have high porosity (approximately 30%) rapidly dissolved within 15 seconds in saliva. Several solvents like cyclohexane, benzene etc. can also be used as pore forming agents. Orodispersible tablets with highly porous structure and good mechanical strength have been developed by this method. (Manoj Ashok Wagh et al 2010)

14

Figure 3: Steps involved in sublimation process (Rakesh Pahwa et al., 2010) Advantages Good physical resistance & highly porous structure Disadvantages Harmful residual adjuvant Extra equipments for heating Not applicable to volatile and heat sensitive drugs. (Priyanka Nagar et al., 2011) Mass extrusion This technology involves softening the active blend using the solvent mixture of water soluble polyethylene glycol, using methanol and expulsion of softened mass through the extruder or syringe to get a cylinder of the product into even segments using heated blade to form tablets. The dried cylinder can also be used to coat granules of bitter tasting drugs and thereby making their bitter taste (Patidar Ashish et al., 2011).

15

Cotton candy process This process is so named as it utilizes an inimitable spinning mechanism to produce floss like crystalline structure, which mimics cotton candy. This technique involves formation of matrix of polysaccharides or saccharides by simultaneous action of flash melting and spinning. The matrix formed is partially recrystallized to have better flow properties and compressibility. This matrix is milled and blended with active ingredients as well as excipients and subsequently compressed to ODTs. This process can accommodate high doses of drug and offers improved mechanical strength. High process temperature limits the use of this process (Rakesh Pahwa et al., 2010). Melt granulation Melt granulation is a process in which pharmaceutical powders are efficiently agglomerated by the use of binder which can be a molten liquid, a solid or a solid that melts during the process. For accomplishing this process, high shear mixers are utilized, where the product temperature is raised above the melting point of binder by a heating jacket or by the heat of friction generated by impeller blades. Perissutti et al prepared carbamazepine fast-release tablets by melt granulation technique using polyethylene glycol 4000 as a melting binder and lactose monohydrate as hydrophilic filler. (Rakesh
Pahwa et al., 2010)

Phase transition Kuno et al proposed a novel method to prepare ODTs with sufficient hardness by involving the phase transition of sugar alcohol. In this technique, ODTs are produced by compressing and subsequently heating tablets that contain two sugar alcohols, one with high and other with a low melting point. Heating process enhances the bonding among particles leading to sufficient hardness of tablets which was otherwise lacking owing to low/little compatibility. (Rakesh Pahwa et al., 2010)

16

Nanonization A recently developed Nanomelt technology involves reduction in the particle size of drug to nano size by wet-milling technique. Surface adsorption of the nano crystals of the drug is done on selected stabilizers for stabilizing them against agglomeration, which are then incorporated into MDTs. This technique is mainly advantageous for poor water soluble drugs and also for a wide range of doses (up to 200 mg of drug per unit). 1.3.7. Important Patented Technologies for Fast Dissolving Tablets (Alok Kumar Gupta et al., 2012) 1. Zydis Technology Zydis formulation is a unique freeze dried tablet in which drug is physically entrapped or dissolved within the matrix of fast dissolving carrier material. When zydis units are put into the mouth, the freeze-dried structure disintegrates instantaneously and does not require water to aid swallowing. The zydis matrix is composed of many material designed to achieve a number of objectives. To impart strength and resilience during handling, polymers such as gelatin, dextran or alginates are incorporated. These form a glossy amorphous structure, which imparts strength. To obtain crystallinity, elegance and hardness, saccharides such as mannitol or sorbitol are incorporated. Water is used in the manufacturing process to ensure production of porous units to achieve rapid disintegration while various gums are used to prevent sedimentation of dispersed drug particles in the manufacturing process. Collapse protectants such as glycine prevent the shrinkage of zydis units during freeze-drying process or long-term storage. Zydis products are packed in blister packs to protect the formulation from moisture in the environment. 2. Durasolv Technology Durasolv is the patented technology of CIMA labs. The tablets made by this technology consist of drug, filler and a lubricant. Tablets are prepared by using conventional tabletting equipment and have good rigidity. These can be packaged into conventional

17

packaging system like blisters. Durasolv is an appropriate technology for product requiring low amounts of active ingredients. 3. Orasolv Technology CIMA labs have developed Orasolv Technology. In this system active medicament is taste masked. It also contains effervescent disintegrating agent. Tablets are made by direct compression technique at low compression force in order to minimize oral dissolution time. Conventional blenders and tablet machine is used to produce the tablets. The tablets produced are soft and friable. 4. Flash Dose Technology Flash dose technology has been patented by fuisz. Nurofen meltlet, a new form of ibuprofen as melt in mouth tablets prepared using flash dose technology is the first commercial product launched by biovail corporation. Flash dose tablets consist of selfbinding shear form matrix termed as floss. Shear form matrices are prepared by flash heat processing. 5. Wow tab Technology Wow tab technology is patented by Yamanouchi Pharmaceutical Co. WOW means Without Water. In this process, combination of low mouldability saccharides and high mouldability saccharides is used to obtain a rapidly melting strong tablet. The active ingredient is mixed with a low mouldability saccharide (eg. lactose, glucose, and mannitol) and granulatedwith a high mouldability saccharide (eg. Maltose,

oligosaccharides) and compressed into tablet. 6. Flash tab Technology Prographarm laboratories have patented the Flash tab technology. Tablet prepared by this system consists of an active ingredient in the form of micro crystals. Drug micro granules may be prepared by using the conventional techniques like coacervation, micro

18

encapsulation and extrusion spheronisation. All the processing, utilized conventional tabletting technology. 1.3.8. Superdisintegrants Disintegrants are substances routinely included in tablet formulations and in some hard shell capsule formulations to promote moisture penetration and dispersion of the matrix of dosage form in dissolution fluids. An oral solid dosage form should ideally disperse into the primary particles from which it was prepared . Superdisintegrants are generally used at a low concentration, typically 1-10% by weight relative to total weight of dosage unit. Generally employed superdisintegrants are croscarmellose sodium (Ac-Di-Sol), crospovidone (CP), sodium starch glycolate (SSG) etc. which represent example of crosslinked cellulose, crosslinked polymer and crosslinked starch respectively. Selection of appropriate formulation excipients and manufacturing technology is necessary for obtaining the optimized design features of orally disintegrating dosage forms. Ideally, superdisintegrants should cause the tablet to disrupt, not only into the granules from which it was compressed but also into powder particles from which the granules were prepared (Rakesh Pahwa et al., 2010). Selection of superdisintegrants Although superdisintegrants primarily affect the rate of disintegration, but when used at high levels they can also affect mouth feel, tablet hardness and friability. Hence, various ideal factors to be considered while selecting an appropriate superdisintegrants for a particular formulation should: Produce rapid disintegration, when tablet comes in contact with saliva in the mouth/oral cavity. Be compactable enough to produce less friable tablets. Produce good mouth feel to the patients. Thus, small particle size is preferred to achieve patient compliance. Have good flow, since it improves the flow characteristics of total blend. (Rakesh Pahwa et al., 2010)

19

Table 1:Superdisintegrants used for the preparation of ODTs (Debjit Bhowmik et al., 2009) Name Composition Mechanism of action Crosscarmellose Ac-Di-Sol Nymce ZSX PrimelloseSolu tab Vivasol L-HPC Crospovidone Crospovidone M Kollidon Polyplasdone Cross linked PVP Swells very little Water insoluble Cross linked cellulose Swells 4-8 folds in < 10 seconds. -Swelling and wicking both. -Swells in two dimensions. -Direct compression or granulation -Starch free Special comment

And returns to original size and spongy in nature after compression but act so get porous tablet by capillary action

Sodium starch glycolate Explotab Primogel Alginic acid NF Satialgine

Cross linked starch

Swells 7-12 folds in < 30 seconds

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

Cross linked alginic acid

-Rapid swelling in aqueous medium or wicking action

-Promote disintegration in both dry or wet granulation

Soy polysaccharides Emcosoy

Natural super disintegrant

-Does not contain any starch or sugar. Used products in nutritional

Calcium silicate

-Wicking action

Highly porous, Optimum concentration is between 20-40%

20

Table 2 : List of commercially available ODTs (Rakesh Pahwa et al., 2010) Product Name Abilify Discmelt Active ingredient Aripiprazole Category Atypical antipsychotics Manufacturer Otsuka America Pharmaceuticals Inc./Bristol-Myers Squibb Co. Alavert ODT Allegra ODT Aricept ODT Loratadine Fexofenadine Donepezil Anti-histamines Anti-histamines Acetylcholinestrase inhibitors Benadryl Allergy Fast Melt Calpol Fast Melts Cibalginadue FAST Clarinex RediTabs Desloratadine Anti-histamines Paracetamol Ibuprofen Diphenhydramine Anti-histamines & anticholinergic Analgesics NSAIDs Pfizer Consumer Healthcare McNeil Healthcare Novartis Consumer Health Schering-Plough Corporation Claratin RediTabs Loratadine Anti-histamines Schering-Plough Corporation Clonazepam ODT Clonazepam Benzodiazepines (Anxiety, Seizure Disorders) Feldene fast melt Piroxicam NSAIDs Pfizer Consumer Healthcare Manza RDT Maxalt-MLT Mirtazapine ODT Olanzapine Rizatriptan Mirtazapine Antipsychotic Triptans/Serotonin Antidepressant Mano Pharma Merck & Co Teva Pharmaceuticals Mosid MT Mosapride 5HT4 agonist Torrent Pharmaceuticals
21

Wyeth Consumer Sanofi Aventis Eisai Inc.

PAR Pharmaceuticals

Nency MD Nulev

Nimesulide Hyoscyamine sulphate

Antipyretic Anticholinergic

Zenon Health Care Schwarz Pharma

Pepcid RPD Reglan ODT Romilast

Famotidine Metoclopramide Montelukast

Antihistamine Antiemetics Antiasthamatic

Merck & Co. Schwarz Pharma Ranbaxy Labs Ltd

Zofran ODT e Zotacet MD

Ondansetron Cetrizine HCl

Antiemetics Antihistamine

GlaxoSmithKlin Zota Pharma

22

You might also like