© 2020 ijrar september 2020, volume 7, issue 3 fast ...ijrar.org/papers/ijrar19l1992.pdf · the...

© 2020 IJRAR September 2020, Volume 7, Issue 3 www.ijrar.org (E-ISSN 2348-1269, P- ISSN 2349-5138)

IJRAR19L1992 International Journal of Research and Analytical Reviews (IJRAR) www.ijrar.org 844

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).

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.”

http://www.ijrar.org/



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

polymer

42-50%

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.

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.

Mechanismof action

Repulsiveforces

Enzymatic action

Swelling

Heat of wetting

capillary action

Relesse of gases




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 :-

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.

Sr.

No.

Natural polymer Marketed

drug

1. Guar Gum Glipizide

2. Fenugreek seed mucilage Metformin

hydrochloride

3. Mango peel pectin Aceclofenac

4. Gellan gum Metronidazole

5. Agar and treated agar Theophylline

6. Gum karaya Amlodipine

7. Chitin and chitosan Cinnarizine

8. Dehydrated banana powder Ondansetron

HCL/

propranolol




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 method

ii) 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 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.

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.




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 loading

ii.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 emulsion

Placed 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 ±10

80-250 ±7.5

250 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 and

slightly merged in medium.

Rotary shaft is used to

provide mechanical stress

and rotation.

Rotational speed,

mechanical stress

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


Force of compression,

medium 0.4 ml water. Room

temperature, measure

beginning and ending of


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 ± 10C

ii) 50 ± 10C

iii) 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 Pharmaceutical

Cibalgina Duefast Ibuprofen Eurand International

Romilast Montelukast Ranbaxy Labs Ltd. Delhi,

India

Acufix DT-TAB Cefixime Macleods, India

Mosid-MT Mosapride citrate Torrent Pharmaceuticals,

Ahmedabad, India

Nimulid MDT Nimesulide Panacea Biotech, New

Delhi, India

Felden fast melt Piroxicam Pfizer Inc. NY, USA

References :-

1. Singh.V. P et.al., Fast Dissolving Tablets “An Opportunity in Novel Drug Delivery System”, World Journal

of Pharmaceutical Research, 2019; 8(8): 465-485.

2. Rahane. R. D, Dr. Rachh.P.R., A Review on Fast Dissolving Tablet, Journal of Drug Delivery and

Therapeutics, 2018; 8(5) :50-55.

3. Santosh K. et.al., Fast Dissolving Tablets – An alternative approach for enhanced therapeutic action, Indo

American Journal of Pharmaceutical Research, 2018, 8(12); 1464-1472.

4. Yadav G., Kapoor A. Fast Dissolving Tablets A Recent Advantages: A Review, International Journal of

Pharmaceutical Sciences and Research, 2012; 3(3): 728-736.

5. Singh. S, Virmani. T, Virmani. R, Mahlawat G. Fast Dissolving Drug Delivery System: Formulation,

Preparation Techniques and Evaluation, Universal Journal of Pharmaceutical Research 2018, 3(4); 56-64.

6. K. Khanna, G. Xavier, Aashish P., Fast Dissolving Tablets: A Novel Approach, International Journal of

Pharmaceutical Research and Allied Sciences 2016, 5(2); 311-322.

7. K. umashankar et.al., Fast Dissolving Tablet: A Review, World Journal of Pharmaceutical Research 2014,

3(6); 424-437.

8. Santosh Kumar et.al., Overview of Fast Dissolving Tablets, Journal of Drug Delivery and Therapeutics, 2019,

9(4-A); 826-830.

9. Patel Zinkal K., Patel Rahul R, A Review: Formulation of Fast Dissolving Tablet, Pharma Tutor, 2014, 2(3);

30-46.

10. Lohithasu D., Shabari Girinath K., Fast Dissolving Dosage Forms: An Overview, World Journal of

Pharmaceutical Research, 2016, 5(10); 1184-2000.




11. Smita Aher, Saudagar R. B., Shinde M. S., Review: Fast Dissolving Tablet, International Journal of current

Pharmaceutical Research, 2018, 10(2); 5-12.

12. D. Bhowmik et.al., Fast Dissolving Tablet: An Overview, Journal of Chemical and Pharmaceutical Research,

2009,1(1); 163-177.

13. Minash Singh Neeraj et.al., ORAL DISPERSIBLE TABLETS: A REVIEW, World Journal of Pharmaceutical

Research, 2017; 6(7): 544-557.

14. Bharpoor Singh et.al., Mouth Dissolving Tablets: An innovative deviation in drug delivery system, J. Pharma.

Sci. & Res. 2019,11(4); 1186-1194.

15. Manish A. et.al., Fast Dissolving Tablets: A Review, International Journal of Current Pharmaceutical

Research, 2017, 9(2) :8-18.

16. Singla. R K., Singla M, Narang N., An Overview on Fast Dissolving Tablet, Webmedcentral Pharmaceutical

Sciences, 2011; 2(12): 1-16.

17. Asija et.al., A Review on Fast Dissolving Drug Delivery System, Int. J. Res. Pharma. Sci, 2014, 4(3); 7-12.

18. Alok Kumar Gupta, Anuj Mittal, Prof. K. K. Jha., Fast Dissolving Tablet: A Review, The Pharma Innovation,

2012, 1(1); 1-8.

19. Dr. Chowdary. Y A., A Review on Fast Dissolving Drug Delivery System – A Pioneering Drug Delivery

Technology, Bull. Env. Pharmacol. Life. Sci. 2012, 1(12); 8-20.

20. Bharti V. P., Strategies to Enhance Solubility and Dissolution of a Poorly Water-Soluble drug, Journal of

Innovations in Pharmaceuticals and Biological Sciences, 2015, 2(4); 482-494.

21. Neena Bedi, Shelly K., Formulation and Evaluation of Mouth Dissolving Tablets of Oxacarbamazepine,

International Journal of Pharmacy and Pharmaceutical Sciences, 2009; 1(1): 12-23.

22. Swapna M, Ritesh B., A Review on -Fast Disintegrating Drug Delivery System, Int. J. Res. Sci. Technol, 2019,

6(1): 291-303.

23. C. H. Jyothi et.al., Formulation and Evaluation of Fast Dissolving Tablets of Zidovudine Using Sublimation

Technique, World Journal of Pharmaceutical Research 2018; 7(13): 912-924.

24. Parameshwara B. P., Md. Rajdar, Formulation and Evaluation of Fast Dissolving Tablets of Nislodipine Using

Different Superdisintegrants, World Journal of Pharmaceutical Research, 2019; 8(7): 1243-1271.

25. Pathak A., Dubey A., Bajpai D., Formulation and Evaluation of Fast Dissolving Tablets of Metformin, World

Journal of Pharmaceutical Research, 2012; 1(2): 174-182.

26. Basu B., Bagadiya A., Makwana S., Formulation and Evaluation of Oxcarbazepine Fast Dissolving Tablets,

Ind. J. Pharma. Sci, 2007, 69(7): 211-214.

27. Neeta et.al., Fast Dissolving Tablets: An Overview, Novel science international journal of pharmaceutical

science, 2012,1(5): 228-232.

28. Errolla Mahesh et.al., Formulation and Evaluation of Montelukast Sodium Fast Dissolving Tablets, Asian

Journal of Biomedical and Pharmaceutical Sciences,2012; 2(14), 75-82.

29. Satpute M. M, Tour N. S., Formulation and In-vitro Evaluation of Fast Dissolving Tablets of Metoprolol

Tartarate,2013, 49(4); 784-792.


© 2020 ijrar september 2020, volume 7, issue 3 fast ...ijrar.org/papers/ijrar19l1992.pdf · the...

Documents