A SHORT REVIEW ON FAST DISSOLVING TABLETS - A NOVEL DRUG DELIVERY SYSTEM

ABOUT AUTHORS:
Yedale A.D.*, Waghmare P.V, Kulkarni S.D., Bhusnure O.G., Bhalekar M.S.
Master of pharmacy, Department of Quality Assurance
Maharashtra College of Pharmacy, Nilanga, dist. Latur (MS) 413521, India
*ajayyedale03@gmail.com

ABSTRACT
Recently, fast-dissolving drug delivery systems have started gaining popularity and acceptance as new drug delivery systems, because they are easy to administer and lead to better patient compliance. Usually, elderly people experience difficulty in swallowing the conventional dosage forms (tablets, capsules, solutions and suspensions) because of tremors of extremities and dysphasia. Fast-dissolving drug delivery systems may offer a solution for these problems. FDTs are those tablets which when placed in mouth get dissolved rapidly in saliva without the need of liquid and can be swallowed. The tablet is the most widely used dosage form because of its convenience in terms of self-administration, compactness, and ease in manufacturing. Fast disintegrating tablets are also known as Fast melting tablets, Orodispersible tablets, fast dissolving/dispersing tablets or melt in mouth tablets. This article reviews the potential benefits offered by FDTs as an oral drug delivery system for various kinds of patients suffering from different diseases and disabilities. Fast dissolving tablets have been formulated for pediatric, geriatric, and bedridden patients and for active patients who are busy and traveling and may not have access to water. Oral delivery is currently the gold standard in the pharmaceutical industry where it is regarded as the safest, most convenient and most economical method of drug delivery having the highest patient compliance. A number of FDDT products for human and veterinary administration are currently under development and the delivery of water soluble as well as lipophilic drug compounds. The excipients that are currently used as well as those that are expected to be used for the future development of improved FDTs are also discussed in this article.

REFERENCE ID: PHARMATUTOR-ART-1738

INTRODUCTION
Fast dissolving dosage forms can be disintegrated, dissolved, or suspended by saliva in the mouth Fast dissolving tablets are useful in patients, like pediatric, geriatric, bedridden, or mentally disabled, who may face difficulty in swallowing conventional tablets or capsules leading to ineffective therapy, with persistent nausea, sudden episodes of allergic attacks, or coughing for those who have an active life style. Fast dissolving tablets are also applicable when local action in the mouth is desirable such as local anesthetic for toothaches, oral ulcers, cold sores, or teething, and to those who cannot swallow intact sustained action tablets/capsules. They provide the convenience of a tablet formulation and also allow the ease of swallowing provided by a liquid formulation. Drinking water plays an important role in the swallowing of oral dosage forms. Often times people experience inconvenience in swallowing conventional dosage forms such as tablet when water is not available, in the case of the motion sickness (kinetosis) and sudden episodes of coughing during the common cold, allergic condition and bronchitis. For these reason, tablets that can rapidly dissolve or disintegrate in the oral cavity have attracted a great deal of attention. Recent technological developments in the dosage form designing the FDTs fulfill the requirement of patient needs without compromising its efficacy. These dosage forms are also used to attain instant a higher concentration of drug in body for immediate actions. Fast dissolving tablets can be prepared by using various conventional methods like direct Compression, wet granulation, moulding, spray drying, freeze drying, and sublimation method and by using different type of superdisintegrants like Cross linked carboxymelhylcellulose (Croscarmeliose),Sodium starch glycolate (Primogel, Explotab), Polyvinylpyrrolidone (Polyplasdone) etc Natural Polymers increased the drug release rate from the tablet, decrease the dissolution and disintegration time, used as binder superdisintegrant, diluent.

Figure 1. Conceptual diagram of FDT

CRITERIA FOR FAST DISSOLVING DRUG DELIVERY SYSTEM:
The tablets should
1. Not require water to swallow, but it should dissolve or disintegrate in the mouth in matter of seconds.
2. Be compatible with taste masking.
3. Be portable without fragility concern.
4. Have a pleasant mouth feel.
5. Leave minimum or no residue in the mouth after oral administration.
6. Exhibit low sensitive to environmental condition as temperature and humidity.
7. Allow the manufacture of the tablet using conventional processing and packaging equipments at low cost.

ADVANTAGES OF FAST DISSOLVING TABLETS
1. Convenient and easy to administer as does not require water for oral administration.
2. Durable and sufficient strength to withstand the rigors of the manufacturing process and manufacturing handling.
3. Pleasant mouth feel.
4. Insensitive to environmental conditions such as humidity and temperature.
5. Improved taste without any residue in the mouth after disintegration.
6. Adaptable and amenable to existing processing and packaging machinery.
7. Cost effective.
8. Compatible with taste masking.
9. Rapid drug therapy intervention.
10. Patient having difficulty in swallowing tablet can easily administer this type of dosage form
11. Useful for pediatric, geriatric and psychiatric patients.
12. Good chemical stability.

DISADVANTAGE OF FAST DISSOLVING TABLETS

1. Fast dissolving tablet is hygroscopic in nature so must be keep in dry place.

2. Some time it possesses mouth feeling.

3. It is also show the fragile, effervesces granules property.

4. FDT requires special packaging for properly stabilization & safety of stable product.²

SALIENT FEATURES OF FAST DISSOLVING TABLETS¹¹

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

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

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

4. Some drugs are absorbed from the pharynx and oesophagus as the saliva passes down into the stomach, in such cases bioavailability of drugs is increased.

5. Ability to provide advantages of liquid medication in form of solid preparation.

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

7. Good mouth feel property helps to change the perception of medication as bitter pill particularly in pediatric patient.

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

9. New business opportunity like product differentiation, product promotion, patent extensions and life cycle management.

10. Beneficial in cases such as motion sickness, sudden episodes of allergic attack or coughing, where an ultra rapid onset of action required.

11. An increased bioavailability, particularly in cases of insoluble and hydrophobic drugs, due to rapid disintegration and dissolution of these tablets.

12. Pre-gastric absorption can result in improved bioavailability and as a result of reduced dosage, improved clinical performance through a reduction of unwanted effects.^2-3

BENEFITS OF FAST DISSOLVING TABLETS

1. Administered without water, anywhere, any time.

2. Suitability for geriatric and pediatric patients, who experience difficulties in swallowing and for the other groups that may experience problems using conventional oral dosage form, due to being mentally ill, the developmentally disable and the patients who are un-cooperative, or are on reduced liquid intake plans or are nauseated.

3. Beneficial in cases such as motion sickness, suede episodes of allergic attack or coughing, where an ultra rapid onset of action required.

4. An increased bioavailability, particularly in cases of insoluble and hydrophobic drugs, due to rapid disintegration and dissolution of these tablets.

5. Stability for longer duration of time, since the drug remains in solid dosage form till it is consumed. So, it combines advantage of solid dosage form in terms of stability and liquid dosage form in terms of bioavailability.

CONVENTIONAL TECHNIQUES FOR FDTs: ^{4, 5, 6}

1. Tablet moulding:
In this method water soluble additives are used to form tablets. The ingredients used in the formulation are passed through the fine mesh, dry blended and wetted with hydroalcoholic solvent and then by using low compression forces compressed into tablets.

2. Freeze drying (Lyophilization):
In this method water is removed by sublimation of the heat sensitive materials and biological. The porous tablets formed having improved absorption and bioavailability.

3. Spray drying:
In this method highly porous fine powders are produced which when compressed into tablets show fast disintegration and enhanced dissolution.

4. Sublimation:
In this method sublime salt is added to the components of tablets and by the process of sublimation the salt is removed and blend is compressed.

5. Addition of disintegrants:
To improve the dissolution and disintegration, disintegrants are added in the FDTs.

6. Direct compression method:
In this method the drug and the excipients are uniformly blended in a prescribed manner and directly compressed into tablet, without any pretreatment. The uniform blend of powders should have good flow properties, the disintegrants are added as excipients in direct compression method.

DRUGS USED IN FAST DISSOLVING DRUG DELIVERY SYSTEM^{7, 12}

Example of some drug candidates best for FDT:

1. Analgesic andante –inflammatory Agents: Ibuprofen, Proxicam, Mefenamic Acid

2.Anti-bacterial Agent-Erythromycin, Tetracycline, Doxycycline,Rifampcin

3.Anti-fungal Agents- Griseofulvin, Miconazole

4.Anti-Malarials-Chlorquine, Amodiaquine

5.Anti-Gout Agent- Allopurinol, Probenecid

6.Anti-Hypertensive -Amlodipine, Nefidipine

7.Anti-Coagulants- Glipizide, Tolbutamide

8. Anti-Protozoal Agents- Benznidazole, Tinidazole

9.Anti-Thyroid agent-Carbimazole

10. Cardiac Inotropic Agent- Digitoxin, Digoxis

11.Gastro-Intestinal Agents- Omeprazole, Ranitidine, Fomatidine

12.Nutritional Agents-Vitamin A, Viitamin B, Vitamin D, etc.

13.Oral Vaccine-Influenza, Hepatitis, Polio, Tuberculosis, etcs.

DESIRED CHARACTERISTICS AND DEVELOPMENT CHALLENGES OF FDTs
Because administration of FDTs is different from administration of conventional tablets, the FDTs should maintain several unique properties, as listed below. ^{8, 9, 10}

A. Fast Disintegration
FDTs should disintegrate in the mouth without additional water or with a very small amount (e.g., 1–2 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 1 minute, but it is preferred to have disintegration as soon as possible.

B. Taste of Active Ingredients
Because FDTs 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 patient acceptance. Unless the drug is tasteless or does not have an undesirable taste, taste-masking techniques should be used. An ideal taste-masking technology should provide drugs without grittiness and with good mouth feel. The amount of taste masking materials used in the dosage forms should be kept low toavoid excessive increase in tablet size. The taste-masking technology should also be compatible with FDT formulations. For example, if drug particles are coated to minimize unpleasant taste, the coating should not be broken during compression or dissolved during wet granulation. Taste masking of bitter tasting drugs is critical to the success of the FDT formulations.

C. Drug Properties
For the ideal FDT technology, the drug properties should not significantly affect the tablet property. Many drug properties could potentially affect the performance of FDTs. For example, the solubility, crystal morphology, particle size, hygroscopicity, compressibility, and bulk density of a drug can significantly affect the final tablet’s characteristics, such as tablet strength and disintegration. The FDT technology should be versatile enough to accommodate unique properties of each drug.

D. Tablet Strength and Porosity
Because FDTs are designed to have a quick dissolution/disintegration time, the tablet porosity is usually maximized to ensure fast water absorption into the tablets. The key properties of the tablets are fast absorption or wetting of water into the tablets and disintegration of associated particles into individual components for fast dissolution. The is requires that excipients should have high wettability, and the tablet structure should also have a highly porous network. Because the strength of a tablet is related to compression pressure, and porosity is inversely related to compression pressure, it is important to find the porosity that allows fast water absorption while maintaining high mechanical strength. In addition, low compression pressure causes fast dissolving dosage forms to be soft, friable, and unsuitable for packaging in conventional blisters or bottles. A strategy to increase tablet mechanical strength without sacrificing tablet porosity or requiring a special packaging to handle fragile tablets should be provided.

E. Moisture Sensitivity
FDTs should have low sensitivity to humidity. This problem can be especially challenging because many highly water-soluble excipients are used in formulation to enhance fast dissolving properties as well as to create good mouth feel. Those highly water-soluble excipients are susceptible to moisture; some will even deliquesce at high humidity. A good package design or other strategy should be created to protect FDTs from various environmental conditions.

DISINTEGRANTS USED IN FDTs:
Some patents use effervescent couples as their disintegrant, while others use a combination of disintegrants. Different types of non-effervescent disintegrants used in the pharmaceutical area.

1. Starch and modified starches. This group includes natural starches (such as maize starch and potato starch), directly compressible starches (such as starch 1500), modifyed starches (such as carboxymethylstarches and sodium starch glycolate), and starch derivatives (such as amylase).

2. Cross-linked polyvinylpyrrolidone

3. Modified celluloses such as cross-linked sodium carboxymethylcellulose

4. Alginic acid and sodium alginate

5. Microcrystalline cellulose

6. Methacrylic acid-divinylbenzene copolymer salts

TECHNIQUES FOR PREPARING FAST DISOLVING TABLETS:
Many techniques have been reported for the formulation of Fast dissolving tablets or Orodispersible tablets.

1. Freeze drying / lyophilization

2. Tablet Moulding

3. Spray drying

4. Sublimation

5. Direct compression

6. Mass extrusion

TABLE 1. Comparison of Technologies for Preparing FDTs¹⁷

Technology

Advantages

Disadvantages

Freeze drying

Immediate dissolution (2-10 s)

Very poor physical resistance

High cost of production

Sensitive to humidity

Low dose of water-soluble drugs

Molding

Very rapid dissolution (5–15 s)

High dose

High cost of production

Weak mechanical strength

Possible limitations in stability

Tableting (standard)

Low cost of production

Use of standard equipment/materials

High dose

Good physical resistance

Significant effects of the size and hardness of the tablets on

disintegration property

Tableting (effervescent)

Use of standard equipment

High dose

Good physical resistance

Pleasant effervescent mouth feel

Operating in controlled low humidity

Need of totally impermeable blister

Tableting (Humidity

Treatment)

Good physical resistance

Pleasant mouth feel

Extra equipments for humidification and drying

Possible limitations in stability

High cost of production

Not suitable for moisture sensitive compounds

Fragile before humidity treatment

Tableting (sublimation)

Good physical resistance Harmful residual adjuvants

Harmful residual adjuvants

Extra equipments for heating

Not applicable to volatile and heat sensitive drugs

FORMULATION OF FAST DISSOLVING TABLETS¹²

Example for Selection of Excipients

1. Superdisintegrants: Crosspovidone, Microcrystallinecellulose, sodium starch glycollate,Sodium carboxy methyl cellulose,pregelatinzed starch, calcium carboxymethyl cellulose, and modified corn starch Sodium starch glycollate has goodflowability than crosscarmellose sodium.Cross povidone is fibrous nature andhighly compactable.

2. Flavours: Peppermint flavour, cooling flavor,flavor oils and flavoring aromatic oil,peppermint oil, clove oil, bay oil, anise oil,eucalyptos oil thyme oil, oil of bitteralmonds. Flavoring agnets include vanilla,citus oils, and fruit essences.

TABLE 2. Flavoring agents for taste masking

Basic Taste	Recommended Flavors
Salt	Butterscotch, maple, apricot, peach, vanilla, wintergreen mint.
Bitter	Wild cherry, walnut, chocolate, mint, anise.
Sweet	Vanilla, fruit and berry.
Sour	Citrus flavor, licorice, root beer, raspberry.

3. Sweetners: Aspartame, Sugars derivatives.

4. Fillers: Directly compressible spray driedMannitol, Sorbitol, xylitol, calciumcarbonate, magnesium carbonate, calciumphosphate, calcium sulfate, pregelatinizedstarch, magnesium trisilicate, aluminumhydroxide.

5. Surface Active Agents: sodiumdoecylsulfate, sodiumlaurylsulfate,Polyoxyethylene sorbitan fatty acid esters(Tweens), sorbitan fatty acid esters(Spans), polyoxyethylene stearates.

6. Lubricants: Stearic acid, Magnesium stearate, Zincstate, calcium state, talc, polyethyleneglycol, liquid paraffin, magnesium laurysulfate, colloidal silicon dioxide.

7. Binder: Polyvinylpyrrolidone(PVP),Polyvinylalcohl(PVA)Hydroxypropy lmethylcellulose(HPMC)

8. Colour: Sunset yellow, Amaranth etc.

NATURAL POLYMERS USED IN FAST DISSOLVING TABLETS:
1.      Aegle marmelos gum (AMG)
2.      Lallemantia reylenne seeds
3.      Locust bean gum
4.      Ficus indica fruit mucilage
5.      Mangifera indica gum24(MIG)
6.      Lepedium Sativum
7.      Hibiscus Rosa sinensis mucilage and treated agar
8.      Dehydrated banana powder (DBP)
9.      Chitosan and Gum Arabic

MECHANISM OF SUPERDISINTEGRANTS:¹³
There are four major mechanisms for tablets disintegration as follows
1. 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.

2. Porosity and Capillary Action (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 disintegrants 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.

Figure 2: Disintegration of Tablet by Wicking and Swelling

3. Due To Disintegrating Particle/Particle Repulsive Forces
Another mechanism of disintegrant attempts to explain the swelling of tablet made with ‘nonswellable’ disintegrants. Guyot-Hermann has proposed a particle repulsion theory based on the observation that nonswelling particle also cause disintegration of tablets. The electric repulsive forces between particles are the mechanism of disintegration and water is required for it. Researchers found that repulsion is secondary to wicking.

4. Due To Deformation
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 breakup of the tablet. This may be a mechanism of starch and has only recently begun to be studied.

Figure 3: Disintegration of Tablet by Deformation and Repulsion

CONCLUSION:
Fast dissolving tablets (FDTs) are prepared by several different methods including crystalline transition, phase transition, sublimation, spray drying, and direct compression. Of these approaches, a conventional tablet compression method is used most widely because of its low cost and ease of manufacturing. The research on FDTs should be focused on decreasing the dissolution time of the tablets in the mouth, while maintaining sufficiently high mechanical strength to withstand handling during manufacturing, packaging and transportation.Natural polymers are preferred over synthetic polymers as they are nontoxic, easily available at low cost used in low concentration and as they are naturally extracted provide nutritional supplement.

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