INTRODUCTION:

Despite of tremendous advancements in drug delivery, the oral route remains the perfect route for the administration of therapeutic agents because the low cost of therapy and ease of administration lead to high levels of patient compliance^1-3. Many patients find it difficult to swallow tablets and hard gelatin capsules and do not take their medicines as prescribed. Difficulty in swallowing or dysphagia is seen to afflict nearly 35% of the general population. Many elderly persons will have difficulties in taking conventional dosage forms (solutions, suspensions, tablets and capsules) because of their hand tremors and dysphagia.

It has been reported that difficulty in swallowing is common among all age groups and more specific with pediatric, geriatric population (because of physiological changes associated with these groups)^4,5 along with institutionalized patients and patients with nausea, vomiting and motion sickness complications⁶. Geriatric and pediatric patients and traveling patients who may not ready access to water are most in needed for easy swallowing dosage forms. Other groups, who may experience problems in swallowing solid dosage forms, are the mentally ill, the developmentally disabled, uncooperative patient and reduced liquid intake plans or nausea. Dysphagia is also associated with number of medical conditions including Stroke, Parkinson’s disease, AIDS, head and neck radiation therapy and other neurological disorders including cerebral palsy. In some cases such as motion sickness, sudden episode of allergic attack or coughing and an unavailability of water, swallowing of tablet or capsules may become difficult. In order to assist these patients, several fast-dissolving drug delivery systems have been developed⁷. Another study shows that an estimated 50 % of the population suffer from this problem. These studies show an urgent need for a new dosage form which will be an effective therapy and can improve patient compliance. As the cost and risk for developing the new chemical entity are becoming higher every year, development of new drug delivery systems for existing drugs can be alternate strategies for many pharmaceutical companies. New drug delivery systems are aimed at improving efficacy and bioavailability of existing drugs, and as well as providing benefits of reducing dosing frequency, minimizing side effects and enhance patient convenience and compliance. Solid dosage form that can be dissolve in or suspended with water in the mouth and result in easy swallowing have a huge marketing potential among the pediatric and geriatric population, as well as other patients who prefer the convenience of readily administered dosage forms. A tablet that dissolves or disintegrates rapidly in oral cavity, resulting in solution or suspension without the need of water is known as FDTs. This novel technology of FDTs is also known as orodispersible tablets, quick disintegrating tablets, mouth dissolving tablets, rapid dissolving tablets, porous tablets, and rapid melts. When this type of tablet is placed into the mouth, the saliva will serve to rapidly dissolve the tablet^8-11.

FDTs disintegrate and/or dissolve rapidly in the saliva without the need for water. Some tablets are designed to dissolve in saliva remarkably fast, within a few seconds and are true fast-dissolving tablets. Others contain agents to enhance the rate of tablet disintegration in the oral cavity and are more appropriately termed fast-disintegrating tablets, as they may take up to a minute to completely disintegrate. When put on tongue, this tablet disintegrates instantaneously, releasing the drug, which dissolves or disperses in the saliva. Some drugs are absorbed from the mouth, pharynx and oesophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablet dosage form. In order to allow FDTs to dissolve in the mouth, they are made of either very porous or soft moulded matrices or compressed into tablets with very low compression force, which makes the tablets friable and/or brittle, which are difficult to handle, often requiring specialized peel-off blister packaging^12-14.

The FDTs provide patients a convenient alternative to traditional tablets or capsules which have to be administered with water or liquid dosage form which is bulkier and less accurate in dose. FDTs are needed for the elderly, children and many others who have difficulty in swallowing.

ADVANTAGES OF FDTS:

FDTs offer all advantages of solid dosage forms and liquid dosage forms along with special advantages, which include:

· As FDTs are unit solid dosage forms, they provide good stability, accurate dosing, easy manufacturing, small packaging size, and easy to handle by patients^{7, 8, 15, 16}.

· No risk of obstruction of dosage form, which is beneficial for traveling patients who do not have access to water.

· Ease of administration to patients who cannot swallow, such as the elderly, stroke victims and bedridden patients; patients who should not swallow, such as renal failure patients; and who refuse to swallow, such as paediatrics, geriatric and psychiatric patients^{17, 18.}

· Rapid disintegration of tablet results in quick dissolution and rapid absorption which provide rapid onset of action⁹.

· Good mouth feel property of FDTs helps to change the basic view of medication as "bitter pill", particularly for paediatric patients due to improved taste of bitter drugs.

· More rapid drug absorption from the pre-gastric area i.e. mouth, pharynx and oesophagus which may produce rapid onset of action^19-22.

· Pregastric absorption of drugs can result in improved bioavailability, reduced dose and improved clinical performance by reducing side effects^{20, 23}.

· New business opportunities: product differentiation, line extension and life-cycle management, exclusivity of product promotion and patent-life extension^18,
19.

Desire Characteristics and Development Challenges of FDTs:

Because administration of FDTs is different from conventional tablets, the FDTs should have a several unique properties to accommodate. Several properties essential to good FDTs are listed below:

Fast Disintegration:

FDTs should disintegrate in the mouth without taking water or with a very small amount (e.g., 1 or 2 mL) of water. The disintegration fluid is provided by the saliva of the patient. The disintegrated tablet should become a soft paste or liquid suspension which can provide good mouth feel and smooth swallowing. The “fast disintegration” usually means disintegration of tablets in less than a minute, but it is preferred to have disintegration in less than 30 seconds.

Taste of the Active Ingredient:

Because fast-dissolve dosage forms dissolve or disintegrate in the patient’s mouth, the drug will be partially dissolved in close proximity to the taste buds. After swallowing, there should be minimal or no residue in the mouth. A pleasant taste inside the mouth becomes critical for patients acceptance. Unless the drug is tasteless or dose not has an undesirable taste, taste masking techniques should be used^{24, 25}. An ideal taste masking technology should prove drugs without grittiness and with good mouth feel. In the meantime, the amount of taste masking materials used in the dosage forms should be kept low to avoid excessive increase in tablet size. The taste masking technology should also be compatible to formulation of FDTs²⁶.

The Drug Property:

For the ideal FDTs technology, the drug properties should not significantly affect the tablets property. Many drug properties could potentially affect the performance of FDTs. For example, solubility, crystal morphology, particle size and bulk density of a drug can affect the final tablet characteristics, such as tablet strength and disintegration²⁷. The fast dissolving tablet technology should be versatile enough to accommodate unique properties of each drug^28-35.

Tablet Strength and Porosity:

Because the fast dissolving dosage form was designed to have quick dissolution/disintegration time, tablet porosity was usually maximized to ensure the water absorption into the tablets. The soft-molded method or tablets compressed at very low compression forces are used in some FDTs technologies to maximize the porosity. However, this causes fast dissolving dosage forms to be soft, friable, and unsuitable for packaging in conventional blisters or bottles. A strategy to increase tablet hardness without sacrificing tablet porosity or requiring a special packaging to handle fragile tablets should be provided^{36, 37}.

Moisture Sensitivity:

FDTs should have low sensitivity to humidity. This problem can be especially challenging because many highly soluble excipients are used in the formulation to enhance fast dissolving properties as well as create good mouth feel. Those highly soluble excipients are susceptible to moisture; some will even deliquesce at high humidity. A good package design or other strategy should be made to protect FDTs from various environmental conditions⁷. Finally, FDTs need be manufactured at low cost.

Formulation Processes for Making FDTs:

The fast-dissolving property of the FDTs is attributed to quick ingress of water into tablet matrix resulting in rapid disintegration. Hence, the basic approaches to develop FDTs include:

· Maximizing the porous structure of the tablet matrix.

· Incorporating the appropriate disintegrating agent/agents.

· Using highly water-soluble excipients in the formulation³⁸

So far, several techniques have been developed on the basis of different principles. The resulting dosage forms vary on grounds like mechanical strength of the final product, drug and dosage form stability, mouth feel, taste, rate of dissolution and absorption from saliva, swallow ability and overall bioavailability. Various processes employed in formulating FDTs includes^39-⁵⁰:

1. Freeze-Drying

2. Moulding

3. Direct Compression

4. Cotton Candy Process

5. Spray Drying

6. Sublimation

7. Mass Extrusion

8. Nanonization

9. Fast Dissolving Films

Table 1 shows the list of various techniques involved in the manufacturing of FDTs.

Approaches for Masking Taste of FDTs:

FDTs, which disintegrate or dissolve in the saliva and produce a positive or negative taste sensation. Most of the drugs have unpalatable taste in which taste masking plays critical role in formulating FDTs. The negative taste sensation of drugs can be reduced or eliminated by various approaches studied, which include addition of sweeteners and flavors, encapsulating the unpleasant drug in to micro particles and adjustment of pH.

Incorporation of Sweeteners and Flavors:

Maximum patient acceptability with FDTs is seen if they provide pleasant taste and mouth feel. To provide this property in tablets various sweeteners and flavors are employed. Usually sugar-based excipients are used as they are highly water soluble and dissolve quickly in saliva and provide pleasant taste and mouth feel to the final product. Mannitol is most widely used excipient in formulating FDTs. Aspartame and citric acid are most commonly used along with various flavor ants such as mint flavor orange flavor, strawberry flavor, peppermint flavor to produce pleasant taste, and mouth feels.

Table: 1 Fast dissolving technique with their processes

FDTs Techniques	Processes	Patented Technology
Freeze-Drying or Lyophilization ^51-61	The water is sublimed from the product after it is frozen. FDTs manufactured using lyophilization process, usually contain excipients like polymers (e.g., gelatin, alginates and dextrin) to provide strength and rigidity to tablets; polysaccharides (e.g., mannitol and sorbitol) to impart crystallinity and hardness to the matrix and to improve palatability; collapse protectants (e.g., glycine) to prevent the product from shrinking in its packaging during manufacturing or storage; flocculating agents (e.g., xanthan gum and acacia) to provide uniform dispersion of drug particles; preservatives (e.g., parabens) to prevent microbial growth; permeation enhancers (e.g., sodium lauryl sulfate) to improve transmucosal permeability; pH adjusters (e.g. citric acid etc.) to optimize chemical stability; flavors and sweeteners to improve patient compliance and water to ensure formation of porous units.	Zydis, Quicksolv and Lyoc
Tablet Moulding ^{62, 63}	Moulded tablets invariably contain water-soluble ingredients due to which the tablets dissolve completely and rapidly. 1. Compression Moulding Process: involves moistening the powder blend with a hydroalcoholic solvent followed by pressing into mould plates to form a wetted mass. 2. Heat-Moulding Process: involves setting the molten mass containing a dispersed drug. 3. Moulding by Vacuum Evaporation without Lyophilization: involves pouring of the drug excipient mixture (in the form of a slurry or paste) into a mould of desired dimension, freezing the mixture to form a solidified matrix and finally subjecting it to vacuum drying at a temperature within the range of its collapse temperature and equilibrium freezing temperature.	Fast Melt
Direct Compression (DC)^64-80	DC is the simplest and most cost effective tablet manufacturing technique for FDTs as they can be fabricated using conventional tablet manufacturing. It is manufactured by using superdisintegrants, Effervescent Agents or Sugar-Based Excipients.( List of superdisintegrants employed in FDTs is mention in Table 2)	Flashtab, Orasolv, Durasolv, Wowtab, Ziplets
Cotton Candy Process^81-88	Is manufactured bu using Shear form™ technology in association with Ceform TI™ technology to eliminate the bitter taste of the medicament. The Shearform technology is employed in the preparation of a matrix known as ‘floss’, made from a combination of excipients, either alone or with drugs.	Flashdose
Spray-Drying	The formulations contained hydrolyzed and unhydrolyzed gelatin as a supporting agent for the matrix, mannitol as a bulking agent and sodium starch glycolate/croscaramellose as a disintegrant. The suspension of above excipients was spray-dried to yield a porous powder which was compressed into tablets. Tablets manufactured by this method disintegrated in < 20 secs in an aqueous medium.
Sublimation^89,90	Sublimation has been used to produce FDTs with high porosity⁸⁹. A porous matrix is formed by compressing the volatile ingredients along with other excipients into tablets, which are finally subjected to a process of sublimation.
Mass-Extrusion⁹¹	involves softening of the active blend using the solvent mixture of water soluble polyethylene glycol and methanol and expulsion of softened mass through the extruder or syringe to get a cylindrical shaped extrude which are finally cut into even segments using heated blade to form tablets. This process can also be used to coat granules of bitter drugs to mask their taste
Nanoniza-tion⁹²	Involves reduction in the particle size of drug to nanosize by milling the drug using a proprietary wet-milling technique.	Advatab
Fast Dissolving Films^93,94	In this technique, a non-aqueous solution is prepared containing water soluble film forming polymer (pullulan, carboxy methylcellulose, hydroxypropyl methylcellulose, hydroxyl ethylcellulose, hydroxyl propylcellulose, polyvinyl pyrrolidone, polyvinyl alcohol or sodium alginate, etc.), drug and other taste masking ingredients, which is allowed to form a film after evaporation of solvent. In case of a bitter drug, resin adsorbate or coated microparticles of the drug can be incorporated into the film

Table 2: List of Superdisintegrants Employed in FDTs

Super disintegrant	Nature	Properties	Mechanism
Crosspovidone	Cross-linked homo polymer of N-vinyl-2-pyrrolidone	Particle size- 100µm	Both swelling and wicking
Cross carmellose Sodium	Cross-linked form of sodium CMC	Insoluble in water, Gives smoother mouth feel, Particle size 200 mesh	Swelling
Sodium starch glycolate	Cross-linked low substituted carboxymethyl ether of poly-glucopyranose	Insoluble in water, Particle size 140 mesh	Water uptake followed by rapid and enormous swelling
Acrylic acid derivatives	Poly(acrylic acid) super porous hydrogel	Insoluble in organic solvents, dispersed in cold water and settles in the form of a highly saturated layer, Particle size 106 µm	Wicking action
Effervescent mixture	Citric acid, tartaric acid, sodium bicarbonate	DT- 15±2 S, crystalline nature	Effervescence
Sodium alginate	Sodium salt of alginic acid	Slowly soluble in water, hygroscopic in nature	Swelling
NS-300	Carboxy methyl cellulose	Particle size 106 µm DT- 20 S	Wicking type
ECG-505	Calcium salt of CMC	Particle size 106 µm DT- 80 S	Swelling type
L-HPC	Low hydroxyl propyl cellulose	Particle size 106 µm DT- 90 S	Both swelling and wicking

Table 3: List of Some of Promising Drug Candidates for FDTs

S. No.	Category	Examples
1.	Antibacterial agents	Ciprofloxacin, tetracycline, erythromycin, rifampicin, penicillin, doxycyclin, nalidixic acid, trimethoprim, sulphacetamide, sulphadiazine etc.
2.	Anthelmintics	Albendazole, mebendazole, thiabendazole, livermectin, praziquantel, pyrantel embonate, dichlorophen etc.
3.	Antidepressants	Trimipramine maleate, nortriptyline HCl, trazodone HCl, amoxapine, mianserin HCl, etc.
4.	Antidiabetics	Glibenclamide, glipizide, tolbutamide, tolazamide, gliclazide, chlorpropamide etc.
5.	Analgesics/anti-inflammatory agents	Diclofenac sodium, ibuprofen, ketoprofen, mefenamic acid, naproxen, oxyphenbutazone, indomethacin, piroxicam, phenylbutazone, etc.
6.	Antihypertensives:	Amlodipine, carvedilol, diltiazem, felodipine, minoxidil, nifedipine, prazosin HCl, nimodipine, terazosin HCl etc.
7.	Antiarrhythmics	Disopyramide, quinidine sulphate, amiodarone HCl, etc.
8.	Antihistamines	Acrivastine, cetrizine, cinnarizine, loratadine, fexofenadine, triprolidine, etc.
9.	Anxiolytics, sedatives hypnotics and neuroleptics	Alprazolam, diazepam, clozapine, amylobarbitone, lorazepam, haloperidol, nitrazepam , midazolam phenobarbitone, thioridazine, oxazepam, etc.
10.	Diuretics	Acetazolamide, clorthiazide, amiloride, furosemide, spironolactone, bumetanide, ethacrynic acid, etc.
11.	Gastro-intestinal agents	Cimetidine, ranitidine HCl, famotidine, domperidone, omeprazole, ondansetron HCl, granisetron HCl, etc.
12.	Corticosteroids	Betamethasone, beclomethasone, hydrocortisone, prednisone, prednisolone, methyl prednisolone, etc.
13.	Antiprotozoal agents	metronidazole, tinidazole, omidazole, benznidazole,

Table 4 - Marketed Products of FDTs

Trade Name	Active Drug	Manufacturer
Nimulid-MD	Nimesulide	Panacea Biotech, New Delhi, India
Feldene Fast Melt	Piroxicam	Pfizer Inc., NY, U.S.A
Zyrof Meltab	Rofecoxib	Zydus, Cadila, India
Pepcid RPD	Famotidine	Merck and Co., NJ, U.S.A
Romilast	Montelukast	Ranbaxy Labs Ltd., New Delhi, India
Torrox MT	Rofecoxib	Torrent Pharmaceuticals, Ahmedabad, India
Olanex Instab	Olanzapine	Ranbaxy Labs Ltd., New Delhi, India
Zofran ODT	Ondansetron	Glaxo Wellcome, Middlesex, UK
Mosid-MT	Mosapride citrate	Torrent Pharmaceuticals, Ahmedabad, India
Febrectol	Paracetamol	Prographarm, Chateauneuf, France
Maxalt MLT	Rizatriptan	Merck and Co., NJ, U.S.A
Zelapar TM	Selegiline	Amarin Corp., London , UK

Encapsulation or Coating of Drugs:

Some of the unpleasant drugs cannot be masked by incorporation of sweeteners and flavors, in such cases alternative method of masking the taste is by encapsulating or coating the drug. In fact this process retards or inhibits dissolution and solubilization of drug, which allows time for particles to pass form mouth before taste is perceived in mouth. List of various drugs explored for developing FDTs and several commercial products available in market for FDTs are given in Table 3 and Table 4 respectively.

Various techniques utilized include

· CIMA'S taste masking technique uses coating of drug with dissolution retarding material⁹⁵

· Phase separation approach for taste-masked microcapsules⁹⁶

· Microcap process used microencapsulation technology⁹⁶

· Extrusion method

· Micro mask technology used casting or spin congealing melt dispersions or solution of drug in molten blend of materials¹

· Flash tab technology⁶⁷

· Solutab technology involves coating drug with sustained release agents, which are finally coated with enteric polymers and further with mannitol⁹⁷

· Blending with cyclodextrins⁹⁸

· Coating crystals, granules, and pellets with aqueous dispersions of meth acrylic acid polymers.

Evaluation of FDTs:

Evaluation parameters of tablets mentioned in the pharmacopoeias need to be assessed, along with some special tests are discussed here.

Hardness/Crushing Strength:

A significant strength of FDTs is difficult to achieve due to the specialized processes and ingredients used in the manufacturing. The limit of crushing strength for FDTs is usually kept in a lower range to facilitate early disintegration in the mouth. The crushing strength of the tablet may be measured using conventional hardness testers.

Friability:

To achieve % friability within limits for FDTs is a challenge to the formulator since all methods of manufacturing of FDTs are responsible for increasing the % friability values. Thus, it is necessary that this parameter should be evaluated and the results are within bound limits (0.1-0.9%).

Wetting Time and Water Absorption Ratio:

Wetting time of dosage form is related with the contact angle. Wetting time of the FDTs is another important parameter, which needs to be assessed to give an insight into the disintegration properties of the tablet. Lower wetting time implies a quicker disintegration of the tablet. The wetting time of the tablets can be measured using a simple procedure. Five circular tissue papers of 10 cm diameter are placed in a petridish with a 10 cm diameter. Ten milliliters of water-soluble dye (eosin) solution is added to petridish. A tablet is carefully placed on the surface of the tissue paper. The time required for water to reach upper surface of the tablet is noted as the wetting time. For measuring water absorption ratio the weight of the tablet before keeping in the petridish is noted (W_b). The wetted tablet from the petridish is taken and reweighed (W_a). The water absorption ratio, R can be then determined according to the following equation:

R = 100 (W_a - W_b)/W_b

Moisture Uptake Studies:

Moisture uptake studies for FDTs should be conducted to assess the stability of the formulation. Ten tablets from each formulation were kept in a desiccators over calcium chloride at 37°C for 24 h. The tablets were then weighed and exposed to 75% relative humidity, at room temperature for 2 weeks. Required humidity was achieved by keeping saturated sodium chloride solution at the bottom of the desiccators for 3 days. One tablet as control (without superdisintegrant) was kept to assess the moisture uptake due to other excipients. Tablets were weighed and the percentage increase in weight was recorded⁹⁹.

Disintegration test:

The time for disintegration of FDTs is generally <1 min and actual disintegration time that patient can experience ranges from 5 to 30 s. The standard procedure of performing disintegration test for these dosage forms has several limitations and they do not suffice the measurement of very short disintegration times. The disintegration test for FDTs should mimic disintegration in mouth with in salivary contents. Various disintegration methods developed are discussed in able 5.

Dissolution test:

The development of dissolution methods for FDTs is comparable to the approach taken for conventional tablets and is practically identical. Dissolution conditions for drugs listed in a pharmacopoeia monograph, is a good place to start with scouting runs for a bioequivalent FDTs. Other media such as 0.1 N HCl and buffers (pH - 4.5 and 6.8) should be evaluated for FDTs much in the same way as conventional tablets. USP dissolution apparatus 1 and 2 can be used. USP 1 Basket apparatus may have certain applications, but sometimes tablet fragments or disintegrated tablet masses may become trapped on the inside top of the basket at the spindle where little or no effective stirring occurs, yielding irreproducible dissolution profiles. Kancke¹⁰⁰ proposed USP 2 Paddle apparatus, which is the most suitable and common choice for FDTs, with a paddle speed of 50 rpm commonly used. Typically, the dissolution of FDTs is very fast when using USP monograph conditions; hence, slower paddle speeds may be utilized to obtain a profile. The USP 2 Paddle apparatus at 50-100 rpm is suitable for dissolution testing of taste-masked drug as well. The media used for the taste-masked drug should match that of the finished product to maximize the value of the test. High-performance liquid chromatography (HPLC) is often required to analyze dissolution aliquots due to presence of UV absorbing components, specifically flavors and sweetener. Excipient to drug ratio may be higher since the formulation is designed to have good taste and mouth feel, decreasing the detection of the drug to background (excipient) in the UV spectrophotometer.

Clinical Studies:

In vivo studies have been performed on oral fast-disintegrating dosage forms to investigate their behavior in the oral–esophageal tract, their pharmacokinetic and therapeutic efficacy, and acceptability. Zydis’s residence time in the mouth and stomach, and its transit through the esophageal tract, was investigated using gamma-scintigraphy. Its dissolution and buccal clearance was rapid, the esophageal transit time and stomach emptying time were comparable with those of traditional tablets, capsules, or liquid forms. A decreased intersubject variability in transit time was also observed^101,
102. Zydis also showed good therapeutic efficacy and patient acceptability - particularly in children^{103, 104} or when easy administration and rapid onset of action were required (such as for patients undergoing surgery)^{105, 106}. The fast disintegrating forms examined showed improved pharmacokinetic characteristics when compared with reference oral solid formulations. For example, the absorption rate of the acetaminophen Flashtab was higher than that of the brand leader, while having the same bioavailability¹⁰⁷. Increased bioavailability and improved patient compliance were observed in Lyoc formulations for different drugs such as phloroglucinol, glafenine, spironolactone, and propyphenazone.

Using Zydis, all the drugs that can be absorbed through the buccal and esophageal mucosa exhibited increased bioavailability and side-effect reduction. This is helpful particularly in actives with marked first-pass hepatic metabolism. Finally, the suitability of FDTs for long-term therapy was also assessed. Lyoc formulations containing aluminum were positively tested in patients with gastrointestinal symptoms¹⁰⁸.

Table 5: In vitro disintegration methods for FDTs

In Vitro Disintegration Method	Characteristic Features	Critical Parameters
Modified USP Apparatus II¹⁰⁹	One liter cylindrical vessel, Paddle as stirring element, basket sinker with FDTs was placed in middle of vessel and hang by a hook to the lid of vessel with distance of 6-8.5 cm	Medium 900 mL, Temp 37⁰C, Paddle, 100 rpm
Rotary shaft method¹¹⁰	Stainless steel wire gauze on which FDTs is placed and slightly immersed in medium. Rotary shaft is employed to provide mechanical stress and rotation.	Rotational speed, Mechanical stress
Sieve method¹¹¹	Glass cylinder with 10-mesh sieve. Device is placed in shaking water bath operated at 150 rpm	Medium 1 mL, Temp. 37⁰C, Shaking speed of water bath
Texture analyzer¹¹¹	Cylindrical flat probe, the bottom of which is adhering by FDTs, which was attached to load cell with very thin layer of glue. FDTs submerged in medium present in beaker or Petridis and compressed. Distance traveled by probe into tablet is measure of disintegration time.	Force of compression, medium 0.4 mL water. Room temperature, measures beginning and ending of disintegration time.
Charge coupled device method¹¹²	Disintegration component and measurement device, which involve continuous acquisition of picture by CCD camera to record disintegration. Plastic cell divided in two parts one component inner tank containing stirring bar, second component is outer tank of thermo stated water	Medium 200 mL, temp. 37 ± 2⁰C

Patient counseling in effective use of FDTs:

FDTs developed offers significant advantages for various group of patients, but the majority of patients receiving FDTs have little understanding of this novel dosage form. Patients receiving FDTs may be surprised when tablets begin to disintegrate/dissolve in mouth. As pharmacists are ideal persons to know about the recent technologies, thus have opportunity to educate the patients for effective treatment. Counseling of patients about this dosage form can avoid any confusion and misunderstanding in taking FDTs. Patient information that needs to be provided includes:

· Storage of this dosage form as some of FDTs developed may not have sufficient mechanical strength, which needs to be handled carefully.

· Patients with Siogren's syndrome or dryness of mouth or who take ant cholinergic drugs may not be suitable candidates for administering FDTs. Although no water is required to allow drug to disperse quickly and efficiently but decreased volume of saliva may slow the rate of disintegration/dissolution and may reduce the bioavailability of the product.

· Patients need to be clearly told about the difference between effervescent and FDTs. Some of technologies use effervescence, which experience a pleasing tingling effect on the tongue.

· Although chewable tablets are available in market and patient need to be counseled about differences between chewable and FDTs tablets. These FDTs can be used easily in children who have lost their primary teeth and in geriatric patients who have lost their teeth permanently. With the pharmacists counseling, intervention and assistance about FDTs, all patients receiving this novel dosage form could be more properly and effectively treated with greater convenience.

Industrial Applications of FDTs:

Industrial applications include the following:

· To develop an orally disintegrating dosage forms and to work with existing disintegrates

· To further improvise upon the existing technology of FDTs

· To optimize the blend of disintegrates or excipients to achieve FDTs

· To select and develop proper packaging material and system for enhanced stability of the product and also develop a cost-effective product

· To arrive at various taste-masking agents and prepare palatable dosage forms thereby increasing patient compliance

· To develop disintegrants from different polymers which are used as coating materials by certain modifications and use them for formulating FDTs

Future Prospects:

These dosage forms may be suitable for the oral delivery of drugs such as protein and peptide-based therapeutics that have limited bioavailability when administered by conventional tablets. These products usually degrade rapidly in the stomach. Should next generation drugs be predominantly protein or peptide based, tablets may no longer be the dominant format for dosing such moieties. Injections generally are not favored for use by patients unless facilitated by sophisticated auto-injectors. Inhalation is one good alternative system to deliver these drugs, but the increased research into biopharmaceuticals so far has generated predominantly chemical entities with low molecular weights. The developments of enhanced oral protein delivery technology by FDTs which may release these drugs in the oral cavity are very promising for the delivery of high molecular weight protein and peptide.

CONCLUSIONS:

FDTs have better patient acceptance and compliance and may offer improved biopharmaceutical properties, improved efficacy, and better safety compared with conventional oral dosage forms. Prescription FDTs products initially were developed to overcome the difficulty in swallowing conventional tablets among pediatric, geriatric, and psychiatric patients with dysphagia. Now a days, FDTs are more widely available as OTC products for the treatment of allergies, cold, and flu symptoms. The target population has expanded to those who want convenient dosing anywhere, anytime, without water. The potential for such dosage forms is promising because of the availability of new technologies combined with strong market acceptance and patient demand. By paying close attention to advances in technologies, pharmaceutical companies can take advantage of FDTs for product line extensions or for first-to-market products. With continued development of new pharmaceutical excipients, one can expect the emergence of more novel technologies for FDTs in the days to come. Thus FDT may be developed for most of the available drugs in near future.

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Received on 22.09.2015 Modified on 15.10.2015

Research J. Pharm. and Tech. 9(1): Jan., 2016; Page 69-78

DOI: 10.5958/0974-360X.2016.00012.3