Fast Dissolving Tablet an Alternative Approach for Enhancement of Oral Bioavailability : A Review

Akshay Bhenki1*, Mithun Maniyar1, Pratiksha Godase2,

1) Department of Pharmaceutics, Shri Vithhal Education Research Institute’s College of Pharmacy, Pandharpur -413304, Dist – Solapur (Maharashtra).

2) Department of Pharmaceutics, SVPM’S College of Pharmacy, Malegaon-413115, Dist- Pune (Maharashtra).

*Corresponding Author: Akshay Bhenki

Department of Pharmaceutics, Shri Vithhal Education Research Institute’s College of Pharmacy, Pandharpur -413304, Dist – Solapur (Maharashtra).

E-mail I’d – akshaybhenki@gmail.com

Fast Dissolving Tablet an Alternative Approach for Enhancement of Oral Bioavailability : A Review

ABSTRACT –

In pharmaceutical industry a lot of modifications and improvisations occurring for patient compliance. In oral drug delivery system improving patient’s compliance is important. Oral drug delivery system is the widely used & It is regarded as safest, most convenient & economical system for drug delivery. Fast Dissolving tablets shows improvement in the dissolution & disintegration property as compare to other tablets. This tablet has high dissolution/disintegration capacity due to which it can easily dissolve in oral cavity with saliva without water. This tablet formulated for pediatric, geriatric and also for bedridden & patients having long travelling. In cases like motion sickness, patients having allergic attacks or an unavailability of water leads to difficulty in administration of conventional dosage form & here the Fast Dissolving Tablet will be useful.

Keywords :- Fast dissolving tablet, Fast dissolving drug delivery, superdisintegrants, Patented technologies

INTRODUCTION (1,2,3)–

The tablets are the mostly used dosage form. It is very easy to administer, does not have any special administration conditions. Also, solid oral dosage form doesn’t require sterile conditions and are therefore, less expensive to manufacture. Patient compliance, High-precision dosing and manufacturing efficiency make tablets the solid dosage forms of choices. One important drawback of such dosage forms is “Dysphagia” or Difficulty in swallowing for geriatric, pediatric and mentally ill patients, most of the patients is affected by such problem, which leads to high non-compliance and ineffective therapy. To overcome this type of problems, scientists found the new drug delivery system. In this system, the tablets show improvement in their dissolution/disintegration rate. Recently, fast disintegrating delivery systems have been started gaining popularity and acceptance as new drug delivery systems. This tablet is also known as Orodispersible tablets, Mouth Disintegrating Tablet or Fast Dissolving Tablet. They are easy to administer and also gives better patient compliance. In some cases, like motion sickness, sudden allergic attacks or coughing and unavailability of water, shows difficulty in swallowing conventional tablets. Mostly pediatric and geriatric patients experience this type of problem. These tablets are of novel types which shows dissolution/disintegration in mouth (Saliva) within seconds in absence of water. According to European Pharmacopoeia, the ODTs should disperse or disintegrate in less tan 3 minutes. The faster the drug into solution, quicker the absorption as well as onset of clinical effects. Some drugs are absorbed from the mouth, Pharynx and esophagus as the saliva passes into the stomach. In such cases, bio availability of drug is significantly greater than those observed from conventional tablets dosage form. Fast dissolution/disintegration of tablets can be achieved by using various methods like Direct compression, wet granulation, compression molding, volatilization and freeze-drying which involves different mechanisms like use of high amounts of hydrophilic disintegrating agents which allow the dosage forms to disintegrate quickly in the patient’s mouth on contact with saliva.

Definition:-

Fast dissolving tablet can be defined as a solid dosage form which dissolves/disintegrates into smaller granules which slowly dissolve in the mouth.

The Center for Drug Evaluation and Research (CDER), US FDA defined Oral Disintegrating Tablets (ODTs) as “A solid dosage form containing medicinal active substance, which disintegrates rapidly, usually within few seconds, after placing it in mouth.”

Benefits of Fast Dissolving Tablet (4,5,6) :-

The tablet doesn’t need water or any other activity. It has better taste masking property It will beneficial for patients having motion sickness, sudden episodes of allergic

attack or coughing. It is easy to administer for those patients who refuse to swallow tablets. It can also be helpful to patients who’s not able to swallow like stroke victims. Disintegrate quickly and rapidly dissolve & absorbed as compared to normal tablet in

oral cavity. Gives quick action of drug. Doesn’t need any special requirement for packing.

Offers improved safety regarding to administration. Ease in portability and provides accurate dosing formulation.

Limitations of Fast Dissolving Tablets (7,3) :-

Carefully handling is must due to their insufficient mechanical strength. Improper manufacturing leads to unfavorable taste & stickiness in mouth. Drugs with high dose are critical to formulate. Drugs having frequent dosing & those require controlled or sustained release are

unsuitable for Fast Dissolving Tablet formulation.

Drug selection Criteria :-

It should have moderately non-ionized at oral cavities pH. It should have low to moderate molecular weight. It should have the ability to permeate the oral mucosa. Drugs having lower bioavailability are good candidates for Fast Dissolving tablets. Short half-life of drugs & frequent dosing drugs is unsuitable. It should be smaller than 50 mg. It should not have bitter taste; it has good solubility in saliva. Drugs used for sustained or controlled release are unsuitable for Fast Dissolving

tablets. Drugs having the capability to diffuse and partition into the epithelium of the upper

GIT (log P > 1, or preferably > 2).

Unique properties of Fast Dissolving Tablets (1,3,4) :-

Fast Dissolving Tablet should,

Easily disintegrate or dissolve with saliva without water. Leave negligible residue in mouth after administration. Portable and easy to transport & packing. Have negligibly sensitive to atmospheric conditions like temperature. Not stick to any inside surfaces of mouth. Suitable with taste masking. Provide better mouth feel after administration.

Need for Development of Fast Dissolving Tablet (9) :-

Suitable for patients who are unable to chew or swallow tablets. Useful for patients use to travel a lot. Drug dissolution in oral cavity avoid first pass metabolism which leads to increase

bioavailability. Improvement of safety regarding administration of drug. Negligible risk of suffocation in airways. Gives quick onset of action which is useful for patients suffering from motion

sickness.

Challenges for formulation Fast Dissolving Tablets (5,7) :-

1. Taste masking :- Some Fast dissolving tablets with undesirable taste couldn’t accepted by patients due to their bitter taste. Rapid disintegrating drug delivery system contains medicaments in taste masked form. But Fast dissolving delivery system disintegrates or dissolves active ingredients in oral cavity & they comes in contact with taste buds. Therefore, taste masking of drugs is critical.

2. Hygroscopicity :- This formulation is hygroscopic in nature which means that it disintegrate/dissolve when comes in contact with water or moisture. Hygroscopicity is become a challenge because of using many highly water-soluble excipients in formulation. Highly water-soluble excipients are susceptible to moisture and hence, design of packaging must be proper to protect Fast dissolving tablets from moisture/atmospheric conditions.

3. Mechanical strength and Disintegration time :-Generally, fast dissolving tablets have less disintegration time. It dissolves/disintegrates quickly in mouth as it comes in contact with saliva and as we know increase in disintegration time leads to lowering of mechanical strength of formulation. That’s why maintaining a balance between both disintegration time and mechanical strength is challenging.

4. Tablet size: - Fast dissolving tablets must have size in between 7-9mm. If tablet size exceeds then it can affect disintegration/dissolution rate.

5. Mouth feel :- After disintegration of fast dissolving tablet, the drug should be in smaller particles in oral cavity for good mouth feel. Addition of flavoring agents also improves mouth feel.

6. Cost :-Any special technologies or methodology for improving fast dissolving tablets may leads to increase in costs of products.

Criteria for selection of excipients:-

It should have quick disintegration. No interaction with drug or other excipients. The melting point of the excipients used in the formulation of fast-dissolving should

be in the range of 30-350C No interference in the efficacy and organoleptic properties of the fast-dissolving

systems. The binder may be in liquid, semi solid, solid or polymeric in nature. Their individual properties should not affect the ODT’S.

Various Ingredients used for Formulation of Fast Dissolving Tablets (8) :-

Table 1 : ingredients with their percentage in formulation

Sr. No.

Types of ingredients Percentage in formulation

1. Active pharmaceutical ingredient 1-25%2. Water soluble film forming

polymer42-50%

3. Plasticizer 0-20%4. Sweetening agent 3-6%5. Saliva stimulating agent 2-6%6. Colors and Flavors 0-10%

1. Super-disintegrants (8,10) :-Super-disintegrants play a vital role in this formulation. Super-disintegrants are the excipient which is formulated for increasing disintegration rate of dosage form. Super-disintegrants are effective at less concentration with greater disintegrating efficiency. Super-disintegrants leads to suck the saliva into the tablet leads to expansion which is helpful for rapid disintegration in oral cavity. Some of the super-disintegrants are sodium starch glycolate, crospovidone, Carmellose, Carmellose calcium, sodium starch glycolate etc.

Types of super-disintegrants on the basis of source :-

i) Natural :- These are some disintegrants which found naturally by plants. e.g. – Chitin and chitosan, Guar gum, Gum Agar

ii) Synthetic :-These are the disintegrants which is formulated by using chemical. e.g. - Microcrystalline Cellulose, Crospovidone, Carmellose.

Ideal characteristics of super-disintegrants :-

An ideal super-disintegrant should have

Poor gel formation. Good hydration capacity Good compressibility & flow property Have no tendency to form complexes with the drugs.

Mechanism of action of super-disintegrants:-

a) By Capillary action :-In this mechanism, primarily all particles of tablet absorb the liquid media and then core of tablet gets penetrated which leads to weakening of inter-particular bond and this leads to breakdown of tablet into smaller particles. Porosity of the tablet is most important factor for quick breaking of tablet. As the material is more porous in nature the less disintegration time.

b) Due to heat of wetting :-Disintegrants mostly have exothermic property, because of this they become wetted and localized stress generated due to capillary air expansion, and this helps to disintegration of the tablet.

c) By swelling :- In this porosity plays a major role, when the super-disintegrants comes in contact with saliva. The aqueous phase applies more adhesion force on superdisintegrant as compared to other excipients & this results in swelling or bursting of tablet.

Mechanism of action

Repulsive forces

Enzymatic action

Swelling

Heat of wetting

capillary action

Relesse of gases

d) By enzymatic action :- The binding property of tablet is destructed by the enzyme which is present in body. This will reduce the binding property & helps to rapid disintegration of tablet.

e) Due to repulsive forces :- According to GUYOT-HERMNN’s “particle explosion theory” non swellable particles can also leads to disintegration of tablet because the electric repulsive force in between particles are act as a disintegration mechanism in presence of water.

f) Due to release of gases :-Carbon dioxide is released when tablet is wetted due to reaction in between Bicarbonate and carbonate with citric acid or tartaric acid. The effervescent mixtures are used to manufacture tablets which having great dissolution or disintegration rate.

Role of Disintegrants :-

Disintegrants play a major role in enhancing disintegration and dissolution of tablet. Super-disintegrants gives rapid disintegration of tablet due to swelling and water

absorption by formulation. Critical concentration of disintegrant is observed during the selection of super-

disintegrant.

Advantages of Disintegrants :-

During formulation it doesn’t stick to the punches and dyes. It is effective in lower concentrations. It gives rapid onset of action as compared to normal tablets.

2. Binders :- Binders are generally used to bind all ingredients with each other during compression process. So, the tablet gets accurate composition without loss of any ingredient. Cellulose polymers, povidones, polyvinyl alcohols & acrylic polymers are commonly used as binders. HydroxyPropylMethylCellulose (HPMC) and Hydroxypropyl Cellulose (HPC) can also used as binders separately or as admixtures.

3. Diluents (Bulking materials) :- These are used to improve bulk properties of drug and it improves texture of tablets that enhances the disintegration of tablet in oral cavity. Bulking materials for this type of formulation should be sugar-based like mannitol, polydextrose, lactose derivatives &starch hydrolysate for greater Aqueous solubility. These are used in formulation in range of 10% about 90% by weight of final composition.

4. Emulsifying Agents :-These agents are helpful in enhancing disintegration and drug release rate. It will also lead to increase bioavailability. Alkyl sulphate, propylene glycol esters are commonly used as emulsifying agent.

5. Flavors and Sweetening Agents :-These agents are mainly used to mask the taste of tablet. Some tablets are bitter in nature but this formulation will dissolves in oral cavity hence the taste of tablets was unaccepted by the patients. And hence by using this agent the bitter taste was masked. Sugar, dextrose & fructose are used as sweetening agent also sodium saccharine & sucralose are used.

Natural Polymers used in Fast Dissolving Tablets :-

Table 3 :- Natural Polymers used in Fast Dissolving Tablets

Advantages of natural polymer used in fast dissolving tablets :-

a) Bio-degradable :- These polymers are found naturally & they all are produced by all living organisms. So, these polymers are biodegradable.

b) Bio-compatible :- All of these are found from plant materials and they are sugar polysaccharides.

c) Environmental-friendly processing :-

Sr. No.

Natural polymer Marketed drug

1. Guar Gum Glipizide2. Fenugreek seed mucilage Metformin

hydrochloride3. Mango peel pectin Aceclofenac4. Gellan gum Metronidazole5. Agar and treated agar Theophylline6. Gum karaya Amlodipine7. Chitin and chitosan Cinnarizine8. Dehydrated banana powder Ondansetron

HCL/ propranolol

A number of varieties of natural polymers obtained from different plants which are widely used by various pharmaceutical companies and it can collected by simple production processes.

d) Local availability :- In India and other developing countries, a large number of promotions has taken by government for production of plants which is used as pharmaceutical excipients.

e) Low cost :-Natural polymers have less production cost. India and other developing countries depends on agriculture, and hence production cost is low and hence the polymers/products are cheaper as compared to synthetic.

Various Methods for formulation of Fast Dissolving Tablets (6,3) :-

A) Non-patented technologies :-

a. Freeze drying (Lyophilization) :- Freeze drying is also known as Lyophilization technique. In this technique, water is sublimed from product after frozen. In this an amorphous porous structure forms which can dissolves/disintegrates rapidly.

Procedure of this technique for formulation of Fast Dissolving Tablet is as follows

Freeze drying technique has improved absorption and bioavailability of tablet. The major disadvantage is that it is time consuming & expensive.

b. Tablet Molding :-Tablet molding technique can be followed by two processes i.e. Solvent method and heat technique. Solid dispersions tablets were prepared by using this technique. Molded tablets have a porous structure which enhances disintegration and easy dissolution occurs. Molded tablets also offer improvement in taste due to presence of water-soluble sugars.

Molded technique is of two types

i) By solvent methodii) By Heat method

1. The active ingredient dissolved into an aqueous

solution of a carrier/polymer.

2. The mixture forms weigh and poured into walls of

blister packs

3. blister packs keep in a tray which is passed

through liquid nitrogen freezing chamber to freeze

the mixture.

4.the frozen blister packs re placed in refrigerated

chambers to continue freezing.

5. After proper freezing drying the aluminium foil backing is

applied on blister-sealing machine.

Solvent method Heat Method

Moisten the drug powder Prepare suspension Blend with a hydroalcoholic that contains a drug, agar solvent sugar (e.g. mannitol)

Compress the powder at low Pour the suspension in pressure in molded plates to form blister packaging wells.

a wetted mass (compression molding) solidify the agar at the

temperature to form a jelly

The solvent is then removed by air and drying at 300C under

Drying. Tablets are packed vacuum. Blister pack the

tablets.

Figure . Procedure of Tablet Molding.

c. Spray Drying :- In this technique, gelatin is used as matrix and a supporting agent, Mannitol as bulking agent and super-disintegrants like croscarmellose or sodium starch glycolate. The tablets are formulated from spray dried powder containing bulking agent, super-disintegrants and acidic ingredient/alkaline ingredients. (sodium Bicarbonate). This reported disintegration within 20 seconds in aqueous medium.

d. Sublimation :-Sublimation is a process in which volatile ingredients are incorporated for production of porous mixture. Highly volatile ingredients like benzoic acid, ammonium bicarbonate, ammonium carbonate, camphor, naphthalene, phthalic anhydride is compressed within tablet with excipients. In sublimation volatile material is removed by leaving highly porous matrix. Tablets formulated by using this technique reported disintegrate within 10-20 seconds.

e. Direct Compression :- Direct compression is the most cost effective and simplest tablet manufacturing technique. The accessibility of improved excipients especially super-disintegrants and sugar-based excipients, this technique can utilize for formulation of Fast Dissolving Tablets.

f. Super-disintegrants :- Super-disintegrants are mainly affects on disintegration and ultimately dissolution tablets, mainly for direct compression technique. The presence of other ingredients such as water-soluble excipients and effervescent agents hastens the disintegration process.

g. Mass Extrusion :- In this technology, the active ingredient is softened by using the water-soluble methanol and polyethylene glycol and subsequent expulsion of softened mass through the extruder or syringe to get a cylinder product and is divided into segments using heated blade to form tablet. The dried cylinder also used as a coat granules.

B) Patented technologies :-

a. Zydis Technology :- Zydis formulation is a unique technology of preparing fast dissolving tablet. It is freeze dried tablet technology in which drug materials are physically entrapped or dissolved within the matrix of fast dissolving carrier materials. Water is not required for swallowing because when “zydis unit” is put in mouth then the freeze-dried structure disintegrates rapidly. Zydis material is composed of so many substances to achieve number of objectives. To provide

1. Drugs and excipients are blended well.

2. The blend is softened using solvent mixture (e.g.

water-soluble polyethylene glycol,

methanol)

3. The softened mass is then extruded via an extruder or syringe.

4. The extrdes are cut into even segments via heated blades to obtain

tablets.

5. The tablets are then coated to taste mask the

bitter taste and packaged.

strength during handling polymers such as dextran, alginate and gelatin are incorporated. Saccharides such as sorbitol or mannitol are incorporated to obtain the good elegance, hardness and crystallinity. To prevent the shrinkage of “zydis unit” during freeze drying process or long term storage glycine is generally used as collapse protectants. To protect the formulation from the moisture it should be packed in a blister.

b. Durasolv Technology :- It is patented technology of CIMA LAB (US patent no. 6,024,981) and is based on direct compression technology which uses suitable excipients with improved properties, especially super-disintegrants that accelerate the rate of disintegration and hence dissolution. This technology is based on employment of conventional non-direct compression fillers (such as dextrose, mannitol, sorbitol etc.) in the form of fine particles that quickly dissolve without producing a gritty or sandy sensation in the mouth. The water soluble and sometimes effervescent agents can also be use that assist in the disintegration process. The Durasolv technology is designed to provide stronger tablets without packaging precautions and can be packed in blisters. In this technology, the tablet consists of drug materials, lubricants and fillers.

c. Orasolv Technology : - CIMA LAB has developed Orasolv technology. It is an effervescent direct compression tablet that disperses in mouth’s saliva with the aid of almost hardly noticeable effervescence and dissolves in less than one minute, leaving the coated drug powder. The unpleasant flavor of the drug is addressed by coating of the drug powder and effervescence. The major disadvantage of Orasolv is its mechanical strength due to light compression. In flash dose technology the matrices are prepared by flash heat processing. This technique is patented by fuisz E.g. nurofen is the first commercial product by this technology launched by BioVil corporation.

d. Wow Technology :- It is patented by Yamanouchi Pharmaceutical corporation where wow tends for “without water”. In this process high mouldability saccharide like oligosaccharide, mannitol, is mixed with low mouldability saccharides like glucose, lactose and mannitol to obtain rapidly melting strong tablet.

e. Shearform Technology :- The core of this technology is preparation of floss. Floss is prepared by subjecting feed stock containing sugar carrier to flash heat process. Sucrose plus either mannitol or dextrose is mixed with surfactant and blended well. This is the primary floss mixture. In flash heat process, the carrier materials show an internal flow condition, which is heat induced and exits via spinning head, and simultaneously under centrifugal force, the floss is flinged. The floss produced by the above way are longer fibers and are further chopped

converting them into smaller particles via a high shear mixture granulator. Recrystallization is completed by use of ethanol treatment (1%), spraying out floss, which subsequent evaporation., which increases flow and cohesive properties. This recrystallized matrix is then mixed with drugs and other excipients and subjected to compression. Tablets produced by this process are highly porous, have a good mouth feel, and have an immediate solubilization of sugar as it comes in contact with saliva.

f. Flashdose Technology: - This technology is much like cotton candy, using a unique spinning mechanism to produce crystalline floss structure. The drug can then incorporated into this crystalline sugar and compressed into a tablet. Such a product has a high surface area for dissolution, dissolving rapidly on tongue and easy dispersion. The Flash dose tablets consist of self-binding shear from matrix termed as “floss”.

g. Ceform Technology :-The crux of this process is placing a dry powder containing pure drug and excipients into a rapidly spinning machine. Centrifugal force of the rotating head of this ceform machine, through small heated opening at high speed blends dry drug powder. This drug blend is liquified to form a sphere, owing to the microburst of heat attained by carefully controlled temperature. This does not affect the stability of the drug. In the preselected oral dosage format, the microspheres are blended and/or compressed.

h. Flashtab Technology :- This technology aims to make the drug have rapid release in GIT, micro encapsulated drug with effervescence, and easily flash dispersal tablet. Usually the polymer used is Eudragit for rapid release. This technology uses conventional approach of wet/dry granulation follow by classical method of compression. Micro-granules of drug, taste masking agents, disintegrating agent, and swelling agents are used to formulate drugs. These tablets have good physical resistance, and highly suggested for hygroscopic materials for blister packing as materials like polyvinylchloride/aluminum foils cater better moisture protection in comparison to conventional polyvinylchloride or polypropylene foils.

i. Nanocrystal Technology :- The technology enhances dissolution rate by decreasing particle size and increasing surface area. Nano-crystal particles are drug particles (less than 1000 nm in diameter), produced by milling the drug substance, and obtained via wt. milling technique. Nanocrystals fast dissolving technology provides, wide range of doses per unit (up to 200mg of API per unit), Based on proprietary and patent-protected technology elements products can be well

classified. Enhanced pharmacokinetics of oral drug. Utilization of non-moisture sensitive in actives, and is economic and cost-effective. Combining drug Nano crystal colloidal dispersions and water-soluble GRAS (Generally Regarded as Safe) ingredients, then filled into blisters, and lyophilized product wafers are formed. They are highly robust, yet dissolve in very small quantities of water in seconds., which is agreeable when working with highly potent or hazardous materials reducing operations, like granulation, blending and tableting. This approach is also enabling small quantity of drugs to be converted into fast dissolving tablets because manufacturing loss is negligible.

j. Advantol 200 :- Specially formulated for nutraceutical applications Advantol 200 is a directly compressible excipients system offering “soft-Melt” functionality and it requires no special manufacturing equipment or tooling. To make robust “soft-melt” tablets it requires standard rotary tablet press with standard tooling under normal tableting temperature and humidity conditions.

k. Advatab :- Advatab technology (Eurand) designed and patented by Kyowa Hakko Kogyo (Tokyo, Japan) produces orally dissolving tablets based on a proprietary tablet composition. Via spray during the production process, each tablet is well lubricated. Advatab is produced using 10-30 times less hydrophobic lubricant and can be 30-40% stronger than conventional tablets.

This result in tablets being:- Hard and durable, yet allows easy wetting upon contact with saliva

i. High drug loadingii. Coated drug particles for better mouth feel

iii. Not require special packaging, and can be packed in conventional packaging systems (push-through blisters and bottles)

iv. Unique as it can be paired with Eurand’s technologies like Microcaps (taste-masking) and Diffucaps (controlled release)

l. Frotsa Technology :- The heart of this technology is producing strong tablets with high porosity via, compression of highly plastic granules at low pressure forming a fast melting tablet. These plastic granules can be classified into three units: a porous and plastic material, enhancer of water penetration, and a binder. A porous, plastic material is water soluble or water dispersible. The inter-particle contacts which is vital to form bonds between particles is improved by plastic deformation of powders. If a porous and plastic material is polymeric. When it comes in contact with the aqueous media it is crucial to avoid formation of a viscous layer of the material at the tablet surface. Better way of making these tablets mix porous, plastic material having water penetration enhancer up to

certain ratios. To prevent formation of a viscous layer on the tablet surface, the porous and plastic particles are separated by water-penetration-enhancing particles. The produced FDTs with desired hardness and fast disintegration time (2 seconds – 30 seconds) depending on the tablet size.

m. Ora-Quick Technology :-The KV Pharmaceutical claims its microsphere technology, known as Micro Mask, utilizing a unique patented taste masking technology. It does not use any type of solvent, thus leading to quicker and more efficient tablet production. It also has lower heat production which is favorable for thermal-sensitive drugs. This technology claims faster dissolutions and better taste masking of tablet. Except for KV pharmaceuticals no other products manufactured by this technology are available in market. This technology evaluates parameters such as: Rate of absorption and dissolution, pleasant mouthfeel, taste, physical strength, bioavailability and stability.

n. Pharma burst Technology :-SPI Pharma, New castle, patents this technology. It utilizes the coprocessor excipients, dissolving within 30-40 seconds. This technology incorporates, dry blending of drug, flavor and lubricant followed by compression into tablets. Tablets produced with sufficient strength, so they can be packed in blister packs and bottles.

o. Lyoc :- Lyoc, is a patented technology of Farmlyoc. The technology aims in producing via lyophilization, a porous and solid galenic of an oil-in-water emulsionPlaced in the blister alveolus. This emulsion paste is ten freezed in blister containing bulk drug or drug microparticles. Loco product has poor mechanical strength due to porosity but good disintegration rate. Example of product is pharmacological Hydrate-Farmlco. Lyco utilizes a freeze-drying process but differ from Zydis in that the product is frozen on the freeze dryer shelves. For prevention of inhomogeneity due to sedimentation during this process, these formulations need a large proportion of undissolved inert filler (mannitol), to enhance the viscosity of the suspension which is processing. This technique produces tablet by direct compression of powdered mixture by using external lubrication.

Evaluation of Fast Dissolving Tablets (9):-

1. Thickness :-Thickness is an important property of tablet in reproducing appearance. It also used in counting during filling equipment usage, some filling equipment’s offers uniformity in thickness of tablets. Thickness can be measured by using micrometer. Generally, 10-20 tablets were taken & their thickness were recorded.

2. Hardness :-

This is measured by using conventional hardness tester (Monsanto tablet hardness tester). In case of Fast Dissolving Tablets, the hardness must lower for faster disintegration process. If hardness is high then it will affect on its disintegration & dissolution rate.

3. Friability :- Getting % friability within the limits for a Fast Dissolving Tablet is a challenge for manufacturer because all methods of formulating of Fast Dissolving Tablet increases the % friability values. So, this parameter should be evaluated & must be recorded within 0.1-0.9%.

4. Weight Variation :-This evaluation is for checking weight of formulated tablets individually.For this evaluation 20-30 tablets were taken randomly from each batch. Weight variation specification as per I.P is as follows

Average weight of tablet % Deviation 80 mg or less ±1080-250 ±7.5250 mg or more ±5

5. Wetting Time :- This method is used to measure tablet wetting time. It was reported by Yunixia et. al., A tissue paper (12 cm × 10.75 cm) folded twice was placed in a Petri dish containing Soreson’s buffer pH 6.8. A tablet was put on paper, and observe till tablet completely gets wetted & record the time at which the tablet wetted completely. This technique performed 2-3 times for each batch.

6. In-vitro Disintegration Test :-In this test, 6 tablets were taken using the apparatus specified in I.P. 1996 distilled water at 370C ± 20C was used as a disintegration media and the time in second is taken for complete disintegration of the tablet without any palatable mass remaining in the apparatus which is to be measured in seconds.

In vitro disintegration method

Characteristic features Critical Parameters

Modified USP apparatus II

1 lit. cylindrical vessel, peddle as stirring element, basket sinker with FDT was placed in middle of vessel and hang by a hook to the lid of vessel with distance 6-8.5 cm.

Medium 900 ml, temperature 370C, paddle 100 rpm

Rotary shaft method Stainless steel wire gauge on. which FDT is placed

Rotational speed, mechanical stress

and slightly merged in medium. Rotary shaft is used to provide mechanical stress and rotation.

Sieve method Glass cylinder with 10 mesh sieve devices is placed in shaking water bath operated at 150 rpm

Medium 1 ml, temperature 370C, shaking speed of water bath

Texture analyzer Cylindrical flat pro the button which is adhered by FDT, which was attached to load cell with very thin layer of glue. FDT submerged in medium present in beaker/ petri dish and compressed. Distance travelled by pro into tablet is measure of disintegration time.

Force of compression, medium 0.4 ml water. Room temperature, measure beginning and ending of disintegration time.

Charge couple device method

Disintegration component and, measurement device which involves continuous acquisition of picture by CCD camera to record disintegration. Plastic cell divided in two parts; One component inner tank containing stirring bath, second compartment is outer tank of thermostated water.

Medium 200 ml, temperature 37±20C

7. Dissolution Test :-Mostly the drugs have dissolution conditions as mentioned in USP monograph. Other media such as 0.1 N HCL, pH 4.5 and pH 6.8 buffers can used for evaluation Fast Dissolving Tablet as same as for ordinary tablet. USP Paddle apparatus is the most suitable and common for evaluation. In this a paddle has the speed of 50 rpm which is commonly used. The dissolution is very fast during evaluation hence slower paddle speed may be utilized to obtain comparative profile. Tablets with large weight (more than 1 gm) may produce mound in dissolution vessel which can prevented by higher paddle speeds.

8. Water absorption ratio :-

A piece of tissue paper folded twice and placed it in a small petri dish having 6 ml of water. A tablet was taken and put it on the paper the time required for complete wetting was measured. The wetted tablet was then weighed. The ratio of water absorption [Water absorption ratio (R)] was calculated by using following equation,

R = 100 (Wa-Wb)/Wb Wb= The weight of the tablet before keeping in the petri dish. Wa = The wetted tablet from the petri dish is taken and reweighed.

9. Stability Study :-

The dissolving tablets stored under the following conditions for a period as prescribed by ICH guidelines for accelerated studies.

i) 40 ± 10Cii) 50 ± 10Ciii) 37 ± 10C and RH 75% ± 5%

Marketed Formulations of Fast Dissolving Tablet (9,11) :-

Brand Name API Company Tempra Quicklets Paracetamol Cima Labs, Inc.Clonazepam Clonazepam Par PharmaceuticalCibalgina Duefast Ibuprofen Eurand InternationalRomilast Montelukast Ranbaxy Labs Ltd. Delhi,

IndiaAcufix DT-TAB Cefixime Macleods, IndiaMosid-MT Mosapride citrate Torrent Pharmaceuticals,

Ahmedabad, IndiaNimulid MDT Nimesulide Panacea Biotech, New

Delhi, IndiaFelden fast melt Piroxicam Pfizer Inc. NY, USA

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