1. INTRODUCTION TO MOUTH DISSOLVING TABLETS:^1-2

Mouth dissolving drug delivery systems (MDDDS) are a new generation of formulations which combine the advantages of both liquid and conventional tablet formulations and at the same time, offer added advantages over both the traditional dosage forms. It provides the convenience of a tablet formulation and allows the ease of swallowing provided by a liquid formulation.

Fast dissolving tablets are also called as mouth-dissolving tablets, melt-in mouth tablets, orodispersible tablets, rapimelts, porous tablets, quick dissolving etc. Fast dissolving tablets are those when put on tongue disintegrate instantaneously releasing the drug which dissolve or disperse in the saliva. The faster the drug into solution, quicker the absorption and onset of clinical effect. Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablets dosage form. The advantage of mouth dissolving dosage forms are increasingly being recognized in both industry and academics. Their growing importance was underlined recently when European pharmacopoeia adopted the term “Orodispersible tablet” as a tablet that to be placed in the mouth where it disperses rapidly before swallowing.

The formulations have special advantages for dysphasic, geriatric, pediatric, bed-ridden, travelling and psychotic patients who are unable to swallow or refuse to swallow conventional oral formulations. It do not require water for administration, thus they are good alternative for travelers and for bed ridden patients. In the recent years, several new advanced technologies have been introduced for the formulation of mouth dissolving tablets (MDTs) with very interesting features, like extremely low disintegration time, exceptional taste masking ability, pleasant mouth feel and sugar free tablets for diabetic patients. The technologies utilized for fabrication of MDDDS include lyophilization, molding, direct compression, cotton candy process, spray drying, sublimation, mass extrusion, and quick dissolve film formation. These techniques are based on the principles of increasing porosity and/or addition of superdisintegrants and water soluble excipients in the tablets. The formulations prepared from these techniques differ from each other on the basis of the factors like mechanical strength of final product, drug and dosage form stability, mouth feel, taste, rate of dissolution of the formulation in saliva, rate of absorption from saliva and overall drug bioavailability. These products not only increase the patient’s compliance but also fetch large revenues to manufacturers due to line extension of the existing formulation. Although, numerous technologies had been developed for the fabrication of these unique dosage forms in last two decades, but so far, no standardized technique has been designed or mentioned in pharmacopoeias for their evaluation except in European Pharmacopoeia (EP), which defines orodispersible tablets as “uncoated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed”. European Pharmacopoeia also specifies that the orodispersible tablets should disintegrate within 3 minutes when subjected to conventional disintegration test used for tablets and capsules.

1.1 Significance of MDTs:^3-6

MDTs offer dual advantages of solid dosage forms and liquid dosage forms along with special features which include:

Ø 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.

Ø Enhanced bioavailability: Bioavailability of drugs is enhanced due to absorption from mouth, pharynx and esophagus.

Ø Rapid action: Fast onset of therapeutic action as tablet gets disintegrated rapidly along with quick dissolution and absorption in oral cavity.

Ø 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 of water.

Ø Ease of administration: Convenient to administer specially for geriatric, pediatric, mentally disabled and bed ridden patients who have difficulty in swallowing.

Ø Obstruction free: No risk of suffocation in airways due to physical obstruction when swallowed, thus providing improved safety and compliance.

Ø Enhanced palatability: Good mouth feel, especially for pediatric patients as taste masking technique is used to avoid the bitter taste of drug.

Ø Simple packaging: No specific packaging required. It can be packaged in push through blisters.

Ø Business avenue: Provide new business opportunities in the form of product differentiation, line extension, uniqueness and life cycle management.

Ø Cost effective: Conventional processing and packaging equipments allow the manufacturing of tablets at low cost.

1.2 Salient Features of MDDS:^7-9

Ø Ease of administration to patients who refuse to swallow a tablet such as pediatric, geriatric and psychiatric patients.

Ø Convenience of administration and accurate dosing as compared to liquids.

Ø No need of water to swallow the dosage form, which is highly convenient especially for patients who are travelling and do not have immediate access to water.

Ø Good mouth feel property of MDDDS helps to change the basic view of medication as “bitter pill”, particularly for pediatric patients.

Ø Rapid dissolution and absorption of drug, which may produce quick onset of action.

Ø Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach; in such cases bioavailability of drugs is increased.

Ø Ability to provide advantages of liquid medication in the form of solid form.

Ø Pregastric absorption can result in improved bioavailability and as a result of reduce dosage and improved clinical performance through a reduction of unwanted effects.

1.3 Requirements of mouth dissolving tablets:

1.3.1 Ideal characteristics of MDTs:^7,8,11,12

MDTs should depict some ideal characteristics to distinguish them from traditional conventional dosage forms. Important desirable characteristics of these dosage forms include:

Ø Require no water for oral administration, yet dissolved or disperse or disintegrate in a matter of seconds.

Ø Provide pleasant feeling in the mouth.

Ø Be compatible with taste masking.

Ø Be portable without fragility concern.

Ø Leave negligible or no residue in the mouth after oral administration.

Ø Exhibit low sensitivity to altered environmental conditions such as humidity and temperature.

Ø Allow high drug loading.

Ø Be harder and less friable.

Ø Allow the manufacture of tablet by using conventional processing and packing equipment.

1.3.2 Advantages of MDT:^8,9

Ø Ease of administration to patient who refuses to swallow a tablet such as pediatric, geriatric and psychiatric patient.

Ø Convenience of administration and accurate dosing as compared to liquid.

Ø No need of water to swallow the dosage form, which is highly convenient feature for patient who are travelling and do not have immediate access to water.

Ø Good mouth feel property of MDT helps to change the basic view of medication as “bitter pill” particularly for pediatric patients.

Ø Rapid dissolution of drug and absorption, which may produce rapid onset of action.

Ø Some drugs are absorbed from the mouth and esophagus as the saliva passes down into the stomach in such cases bioavailability of drug is increased.

Ø Ability to provide advantage of liquid medication in the form of solid preparation.

Ø Pre-gastric absorption can result in improved bioavailability and as a result of reduced dosage improved clinical performance through a reduction of unwanted effect.

Ø Achieve increased bioavailability/rapid absorption through pre-gastric absorption of drug from mouth, pharynx and esophagus as saliva passes down.

Ø The risk of chocking or suffocation during oral administration of conventional formulation due to physical obstruction is avoided, thus providing improved safety.

Ø New business opportunity like product differentiation, product promotion, patent extension and life cycle management.

1.3.3 Disadvantages of MDT:^8,9

Ø The tablets usually have insufficient mechanical strength. Hence careful handling is required.

Ø The tablets may leave unpleasant taste and/or grittiness in mouth if not formulated properly.

Ø Tablets are very fragile and lack physical resistance. Because the tablets are very porous and low compression forces are used to prepare them. They cannot be packed in conventional strips or in bottles and special packaging is required.

Ø Bitter drugs have to be taste masked by various techniques which in turn increases the time and cost of production.

Ø Their growing importance of fast dissolving /disintegrating tablet was under lined recently when European Pharmacopoeia adopted the term “Oro-dispersible Tablet” as a tablet that to be placed in the mouth where it disperses rapidly before swallowing.

1.4 Challenges in formulating mouth dissolving tablets:

· Palatability:^10,11

As most drugs are unpalatable, orally disintegrating drug delivery systems usually contain the medicament in a taste-masked form. Delivery systems disintegrate or dissolve in patients oral cavity, thus releasing the active ingredients which come in contact with the taste buds; hence, taste-masking of the drugs becomes critical to patient compliance.

· Mechanical strength:¹²

In order to allow FDTs to disintegrate in the oral cavity, they are made of either very porous and soft-molded matrices or compressed into tablets with very low compression force, which makes the tablets friable and/or brittle, difficult to handle and often requiring specialized peel-off blister packing that may add to the cost. Only few technologies can produce tablets that are sufficiently hard and durable to allow them to be packaged in multidose bottles, such as Wowtab® by Yamanouchi-Shakleeand DuraSolv® by CIMA labs.

· Hygroscopicity:^10,13

Several fast dissolving dosage forms are hygroscopic and cannot maintain physical integrity under normal conditions of temperature and humidity. Hence, they need protection from humidity which calls for specialized product packaging.

· Amount of drug:¹³

The application of technologies used for OFTs is limited by the amount of drug that can be incorporated into each unit dose. For lyophilized dosage forms, the drug dose must be lower than 400 mg for insoluble drugs and less than 60 mg for soluble drugs. This parameter is particularly challenging when formulating a fast-dissolving oral films or wafers.

· Aqueous solubility:¹⁴

Soluble drugs pose various formulation challenges because they form eutectic mixtures, which result in freezing-point depression and the formation of a glassy solid that may collapse upon drying because of loss of supporting structure during the sublimation process. Such collapse sometimes can be prevented by using various matrix-forming excipients such as mannitol than can induce crystallinity and hence, impart rigidity to the amorphous composite.

· Size of tablet:¹²

The degree of ease when taking a tablet depends on its size. It has been reported that the easiest size of tablet to swallow is 7-8 mm while the easiest size to handle was one larger than 8 mm. Therefore, the tablet size is both easy to take and easy to handle.

1.5 Superdisintegrants:^8,13

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 crosscarmellose sodium (Ac-Di-Sol), crosspovidone (CP), sodium starch glycolate (SSG), Indion 414 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.

1.5.1 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:

Ø Produce rapid disintegration, when tablet comes in contact with saliva in the mouth/oral cavity.

Ø Be compactable enough to produce less friable tablets.

Ø Produce good mouth feel to the patients. Thus, small particle size is preferred to achieve patient compliance.

Ø Have good flow, since it improves the flow characteristics of total blend.

1.5.2 Mechanism of action of superdisintegrants:

The tablet breaks to primary particles by one or more of the mechanisms listed below:-

· Capillary action/Water wicking

· Swelling

· Heat of wetting

· Disintegrating particle/particle repulsive forces

· Deformation

· Release of gases

· Enzymatic action

Ø Capillary action / Water wicking:

Disintegration by capillary action is always the first step. When we put the tablet into suitable aqueous medium, the medium penetrates into the tablet and replaces the air adsorbed on the particles, which weakens the intermolecular bond and breaks the tablet into fine particles. Water uptake by tablet depends upon hydrophilicity of the drug /excipients and on tableting conditions. For these types of disintegrates maintenance of porous structure and low interfacial tension towards aqueous fluid is necessary which helps in disintegration by creating a hydrophilic network around the drug particles.

Ø Swelling:

Perhaps the most widely accepted general mechanism of action for tablet disintegration is swelling. Tablets with high porosity show poor disintegration due to lack of adequate swelling force. On the other hand, sufficient swelling force is exerted in the tablet with low porosity. It is worthwhile to note that if the packing fraction is very high, fluid is unable to penetrate in the tablet and disintegration is again slows down.

Fig 1.1 Disintegration of tablet by wicking and swelling

Ø Heat of wetting (air expansion):

When disintegrates with exothermic properties gets wetted, localized stress is generated due to capillary air expansion, which helps in disintegration of tablet. This explanation however, is limited to only a few types of disintegrates and cannot describe the action of most modern disintegrating agents.

Ø Disintegrating particle / Particle repulsive forces:

Another mechanism of disintegration attempts to explain the swelling of tablet made with ‘non-swellable’ disintegrates. Guyot-Hermann has proposed a particle repulsion theory based on the observation that non-swelling particle also cause disintegration of tablet. 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.

Ø 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. This increase in size of the deformed particles produces a break tablet.

Fig 1.2 Disintegration by deformation and repulsion

Ø 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 disintegrates are highly sensitive to small changes in humidity and temperature level, 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.

Ø Enzymatic reaction:

Here the enzymes presents in the body act as disintegrates. These enzymes destroy the binding action of binder and helps in disintegration.

Table 1.1 Disintegrating enzymes.

ENZYMES	BINDER
Amylase	Starch
Protease	Gelatin
Cellulose	Cellulose and its derivatives
Invertase	Sucrose

1.6 Techniques for preparing mouth dissolving tablets:^15,16,17

1.6.1 Freeze Drying:^{1, 14-16}

A process, which involves sublimation of water from the product after freezing is called freeze drying. Freeze dried forms offer more rapid dissolution than other available solid products as process imparts glossy amorphous structure to the bulking agent and sometimes to the drugs. A tablet that rapidly disintegrates in aqueous solution includes a partially collapsed matrix network that has been vacuum dried above the collapse temperature of the matrix. The matrix is partially dried below the equilibrium freezing point of the matrix. Vacuum drying of the tablet above its collapse temperature instead of freeze drying below its collapse temperature provides a process for producing tablets with enhanced structural integrity, while rapidly disintegrating in normal amounts of saliva. However the user of freeze drying is limited due to high cost of equipment and processing. Other major disadvantages of the final dosage forms include lack of physical resistance in standard blister packs.

1.6.2 Molding:

Mould ability is defined as the capacity of the compound to get molded or compressed. Low mould ability means that the compound show reduced compressibility by tabletting and rapid dissolution while high molding compounds show excellent compressibility and slow dissolution. Tablets produced by molding are solid dispersions. Physical forms of the drug in the tablets depend whether and to what extent it dissolves in the molten carrier. The drug can exist as discrete particles or micro particles dispersed in the matrix. It can dissolve totally in the molten carrier to form solid solution or dissolve partially in the molten carrier and the remaining particles stay undissolved and dispersed in the matrix. Disintegration time, drug dissolution rate and mouth feel will depend on the type of dispersion or dissolution. Molded tablets disintegrate more rapidly and offer improved taste because the dispersion matrix is generally made from water soluble sugars.

1.6.2.1 Types of molded tablets:¹⁵

Ø Compression molding:

Compressed molded tablets are prepared from soluble ingredients by compressing a powder mixture previously moistened with solvent (usually water or ethanol) into mould plates to form wetted mass.

Ø Heat molding:

In this, molded form have been prepared directly from the molten matrix in which drug is dissolved or dispersed.

Ø No-vacuum lyophilization:

Molded form prepare by no-vacuum evaporation method involves evaporation of solvent from the suspension at standard pressure.

T. Makino et al. Have developed compression molded mixtures containing drug and combination of starches and sugars with surfaces that have been wetted with suitable amount of water. The wetted mass is compression molded and dried porous tablets with sufficient mechanical strength have been obtained.

Molded tablets typically do not possess great mechanical strength. Erosion and breakage of the molded tablet often occur during handling and opening of blister packs.

1.6.3 Sublimation:^14-16

Compressed tablets composed of highly water-insoluble excipients do not dissolve rapidly in the water because of its low porosity, so porous tablets that exhibit good mechanical strength and dissolve quickly is the best remedy for above problem.

Heinemann and Rose et.al. have produced porous tablet by addition of inert solid ingredients such as urea, urethane, ammonium carbonate, camphor, naphthalene with other tablet excipients and the blend was compressed into tablet. Then volatile material from compressed tablet is removed by sublimation so as to impart porosity to tablet.

A method of producing fast dissolving tablet using water as the pore forming material has been described by Makino etal, Koizumi, etal. have developed a new method of preparing high porosity tablet that dissolve rapidly within 10-20 seconds and exhibit sufficient mechanical strength using mannitol with camphor, a subliming material.

Fig 1.3 Sublimation method

1.6.4 Spray drying:^14-16

As the processing solvent is evaporated rapidly during spray drying, it gives highly porous and fine powders. Allen and Wang have employed spray drying technique to prepare fast dissolving tablets. They developed formulation by using mannitol as bulking agent, hydrolyzed and non-hydrolyzed gelatin as support matrix, sodium starch glycolate as disintegrant and acidic material (e.g.NaHCO₃) to enhance disintegration and dissolution. When immersed in an aqueous medium, the tablets compressed from spray-dried powder, disintegrated within 20 seconds.

1.6.5 Mass Extrusion:^11-16

In this technology, the active blend is softened by using the solvent mixture of water soluble polyethylene glycol, methanol and then softened mass is expulsed through the extruder or syringe to get a cylinder of the product into even segment using heated blade to form tablets. The dried cylinder can also be used to coat granules of bitter tasting drug in order to mask their bitter taste.

1.6.6 Direct Compression:^{16- 17}

Direct compression is the easiest way to manufacture tablets. It can be done with conventional equipment, commonly available excipients and a limited number of processing steps. It also allows to accommodate high dose and final weight of tablet can easily exceed that of the other production methods.

Direct compressed tablet disintegration and solubilization depends on various factor such as single or combined action of disintegrates, water soluble excipients and effervescent agent. Disintegrant efficacy is based on force equivalent concept, which is the combined measurement of swelling force development and amount of water absorption and defines the capability of disintegrant to transform absorbed water into swelling force. Disintegrant efficacy is strong affected by tablet size and hardness. Large and hard tablet require more disintegration time. As consequences, products with optimal disintegration properties often have medium to small size and high friability and low hardness. The tablet with high friability and low hardness has less physical resistance, which cause breakage of tablet edges during the opening of blister alveolus.

Mouth dissolving tablet prepared by direct compression method involves use of superdisintegrants. Superdisintegrants are the agent, which are completely effective in very low concentration (2-4%). So to ensure a high disintegration rate of MDT, choice of suitable type and an optimal amount of disintegrant is important. Other formulation components such as water-soluble excipients or effervescent agent can further enhance dissolution or disintegration properties but main drawback of using effervescent excipients is their highly hygroscopic in nature.

The simultaneous presence of disintegrant with a high swelling force called disintegrating agent and substances with low swelling force (starch, cellulose and direct compression sugar) defined as “swelling agent” was claimed to be a key factor for rapid disintegration of tablet, which also offers physical resistance to tablet.

1.6.7 Crystalline transition method:¹⁶

The crystalline transition method (CTM) makes use of the phase transition of pharmaceutical excipients, especially sugars, from the amorphous to crystalline state to improve tablet mechanical strength while maintaining porosity. Amorphous forms of sugars have higher compressibility than crystalline forms, so they can contribute to high tablet porosity. However, amorphous sugars have a tendency to absorb more moisture than crystalline ones, which means that the tablets containing amorphous sugars are more sensitive to moisture.

Fig 1.4 Crystalline transition method

1.6.8 Sugar based excipients:

This is another approach to manufacture ODT by direct compression. The use of sugar based excipients especially bulking agents like dextrose, fructose, isomalt, lactilol, maltilol, maltose, mannitol, sorbitol, starch hydrolysate, poly-dextrose and xylitol, which display high aqueous solubility and sweetness. Hence, impart taste masking property and a pleasing mouth feel. Mizumito et al have classified sugar-based excipients into two types on the basis of molding and dissolution rate.

Type 1 saccharides (lactose and Mannitol) exhibit low mould ability and high dissolution rate.

Type 2 saccharides (maltose and maltilol) exhibit high mould ability and low dissolution rate.

Fig 1.5 Compression of sugar based excipients

1.6.9 Cotton candy process:

The cotton candy process is also known as the “candy floss” process and forms the basis of the technologies such as Flash Dose (Fuisz Technology). A fast dissolving tablets are formed using a candyfloss or shear form matrix, the matrix is formed from saccharides or polysaccharides processed into amorphous floss by a simultaneous action of flash melting and centrifugal force. The matrix is then cured or partially recrystallised to provide a compound with good flow properties and compressibility. The candyfloss can then be milled and blended with active ingredients and other excipients and subsequently compressed into fast dissolving tablets. However the high processing temperature limits the use of this technology to thermo stable compounds only.

1.7 Patented technology for mouth dissolving tablets:^18-20

1.7.1 Zydis technology:^1,14,17,18

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 required water to aid swallowing. The Zydis matrix is composing of many materials designing to achieve a number of objectives. To impart strength and resilience during handling, polymer such as gelatin, dextran or alginates are incorporated. These form a glossy amorphous structure, which impart strength.

To obtain crystallinity, elegance and hardness, saccharide 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 formulation from moisture in the environment.

1.7.2 Durasolv technology:^1,14,17,18

Durasolv is the patented technology of CIMA labs. The tablets made by this technology consist of drug, filler and lubricant. Tablets are prepared by using conventional tabletting equipment and have good rigidity. These can be packaged into conventional packaging system like blisters. Durasolv is an appropriate technology for product requiring low amount of active ingredients.

1.7.3 Orasolv technology:^1,14,17,18

CIMA labs have developed Orasolv technology. In this system active medicament is taste masked. It also contain 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 produce are soft and friable and place system.

1.7.4 Flash dose technology:¹⁷

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 self-binding shear form matrix termed as “Floss shear” form matrices are prepared by flash heat processing.

1.7.5 Wowtab Technology:¹⁷

Wowtab technology is patented by Yamanouchi Pharmaceutical Co. WOW means “Without Water”. In this process, combination of low mouldability saccharide and high mouldability saccharide is used to obtain a rapidly melting strong tablet.

The active ingredient is the mixed with a low mouldability saccharide and granulated with a high mouldability saccharide and compressed into tablet.

1.7.6 Flashtab Technology:¹⁷

Prographarm laboratory have patented the Flashtab technology. Tablet prepared by this system consist of active ingredient in the form of Micro crystals. Drug micro granules may be prepared by using the conventional techniques like co-acervation, micro encapsulation and extrusion-spheronisation. All the processing utilized conventional tableting technology.

Table 1.2 A list of patented technologies using manufacturing techniques and description

Technology	Basic of technology	Company
Zydis	Lyophilization	R. P. Scherer Inc.
Durasolv	Compressed tablets	cima Labs Inc.
Orasolv	Compressed tablets	Cima Labs Inc.
Flash dose technology	Cotton candy process	Fuisz Technology Ltd.
Wowtab	Compressed molded tablets	Yamanouchi PharmaTechnologies, Inc
Flashtab	Multiparticulate compressed tablets	Ethypharm

Table 1.3 List of marketed preparation of MDT

Trade name	Active drug	Manufacturer
Nimulid : MD	Nimesulide	Panacea Biotech
Feldene fast melt	Piroxicam	Pfizer Inc
Zyrof meltab	Rofecoxib	Zydus Cadila
Pepcid RPD	Famotidine	Merck and Co.
Romilast	Montelukast	Ranbaxy Labs Ltd
Ondem MD	ondencetrom	Alkem pharma
Mosid md	Mosapride	Torrent pharma
valus	Valdecoxib	Galen mark
Vomidon md	Domperidone	Olcare lab
Lonazep MD	Olnazepine	Sun pharma
Zelapar TM	Selegiline	Elanl Amarin corporation
Febrectol	Paracetamol	Prographarm, Chateauneuf

2. CONCLUSION:

Recently there is significant amount of non-compliance among the patients and hence there is a need to design the patient-oriented drug delivery systems. Orally disintegrating tablets have better patient acceptance and offer improved biopharmaceutical properties, improved efficacy and better safety as compared with conventional oral dosage forms. Recent trends of patient oriented dosage form to achieve patient compliance.

By using new manufacturing technologies, many drugs can be formulated in the form of mouth dissolving tablets to provide the advantages of liquid medication in the form of solid preparation. FDT need to be formulated for pediatric, geriatric, bedridden, psychotic patients, for those patients who are busy in traveling, patients who are may not have access to water.

The key to FDT formulations is fast disintegration, dissolution, or melting in the mouth, and this can be achieved by producing the porous structure of the tablet matrix or adding superdisintegrant and/or effervescent excipients. The clinical studies show FDTs can improve patient compliance, provide a rapid onset time of action, and increase bioavailability. Considering the many benefits of FDTs, it is only a matter of time until a majority of oral formulations are prepared in FDT forms.

3. FUTURE PROSPECTS AND RESEARCH TRENDS IN MDT:

There are several biopharmaceutical advantages such as improved efficiency over conventional dosage forms for Mouth dissolving tablets. For example, they require smaller amounts of active ingredient to be effective, improve absorption profiles, and offer better drug bioavailability than regular tablets and capsules. There are still many aspects to improve in the FDT formulations.

Despite advances in the FDT technologies, formulation of hydrophobic drugs is still a challenge, especially when the amount of drug is high. The low dose drugs, such as loratadine with 10 mg dose, pose little problem, but as the dose increases, the formulation sacrifices its fast disintegrating property. A new technology is being developed to incorporate higher doses of hydrophobic drugs without affecting the fast disintegrating property too severely.

The disintegration times of most FDTs on the market are acceptable i.e., less than 60 seconds but certainly there is a room for improvement. Because the disintegration time is related to other formulation variables, a balance has to be maintained between shortening the disintegration time and other tablet properties. The tablet hardness, friability, and stability can be further improved to such a level that multi tablet packaging in conventional bottles becomes a norm.

The future of FDTs lies in the development of mouth dissolving tablet with controlled release properties. If one FDT can deliver drugs with short half-lives for 12-24 hours, it would be a quantum improvement in the FDT technology. The added convenience and compliance of such formulations would be enormous.

The future of FDTs also lies in the development of effective taste-masking properties. The use of coating poorly tasting drugs is commonly used, but it increases the total volume of the final formulation.

There may be no magic solution to this, but more effective use of existing taste masking technologies is expected to alleviate the problems associated with taste masking.

The safety and efficacy profile of drugs in orodispersible tablet is same like their conventional tablet dosage form. Based on conventional techniques, new techniques are developed like Zydis, Wow Tab, Flashtab technology and many more, which leads to getting a patent and new market strategy for orodispersible tablets. This dosage form are gaining market share day by day and becoming a better choice of acceptance.

In addition, the ability to formulate drugs in large doses will bring another important technological advance. In general, the FDT formulations require large amounts of excipients, and having large doses of drug will only make the final formulation too big to handle. FDT formulations that would require fewer excipients than the drug itself would be a breakthrough. While the problems to be solved are not easy, the history suggests that it is just a matter of time before they are solved.

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Received on 10.02.2016 Modified on 18.03.2016

Research J. Pharm. and Tech. 9(3): Mar., 2016; Page 287-295

DOI: 10.5958/0974-360X.2016.00053.6