93 | P a g e International Standard Serial Number (ISSN ...ijupbs.com/Uploads/8. RPA1415111015.pdf · This segment of formulation is especially dosing for dysphagic, geriatric, pediatric

93 | P a g e International Standard Serial Number (ISSN): 2319-8141

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International Journal of Universal Pharmacy and Bio Sciences 3(4): July-August 2014

INTERNATIONAL JOURNAL OF UNIVERSAL

PHARMACY AND BIO SCIENCES IMPACT FACTOR 1.89***

ICV 5.13*** Pharmaceutical Sciences REVIEW ARTICLE……!!!

A REVIEW ON IMMEDIATE RELEASE TABLET

Zaz Saba Abdulraheman*, Dr. M.R. Patel, Dr. K. R. Patel

Shri B.M Shah College of Pharmaceutical Education and Research, Modasa (Arvalli):- 383315.

KEYWORDS:

Patient compliance,

Tablets and Capsules,

Immediate release tablet.

For Correspondence:

Zaz Saba Abdulraheman*

Address: Department of

Pharmaceutics, Shri B.M

Shah College of

Pharmaceutical

Education and Research,

Dhansura road College

campus Modasa,

Dist.: Arvalli,

Pin code: 383315,

Gujarat, India.

E mail id:

[email protected]

ABSTRACT

Methods to improve patient‟s compliance have always attracted

scientists towards the development of fancy oral drug delivery. Oral

routes of drug administration have wide acceptance up to 50-60%

of total dosage forms. Solid dosage forms are popular because of

ease of administration, accurate dosage, self-medication, pain

avoidance and most importantly the patient compliance. The most

popular solid dosage forms are being tablets and capsules; one

important drawback of this dosage forms for some patients, is the

difficulty to swallow. 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. This tablet format is

designed to allow administration of an oral solid dose form in the

absence of water or fluid intake. Several techniques have been

developed in the recent past, to improve the disintegration quality of

these delicate dosage forms without affecting their integrity.

Immediate release tablet have the unique property of rapidly

disintegrating and/or dissolving and generally within <60 Seconds

without the need of water, thus obviating the requirement of water

during administration. Immediate release tablet have been

formulated for pediatric, geriatric, and bedridden patients, patients

who are uncooperative, and for active patients who are busy and

traveling and may not have access to water. Apart from the

conventional methods of fabrication, this review also provides the

detailed concept with their advantages and limitations.

mailto:[email protected]



INTRODUCTION:

Fast dissolving dosage forms can be disintegrated, dissolved, or suspended by saliva in the mouth.

Fast dissolving tables are useful in patients, like pediatric, geriatric, bedridden, or mentally disabled,

who may face difficulty in swallowing conventional tablets or capsules leading with persistent

nausea sudden episodes of allergic attacks or coughing for those who have an active life style. Fast

dissolving tablets are also application 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 sustained action tablets/capsules. offer the luxury of much more accurate dosing

than the primary alternative, oral liquid.

This segment of formulation is especially dosing for dysphagic, geriatric, pediatric bed-ridden

travelling and psychotic patients who are unable to swallow or refuse to swallow conventional oral

formulations. As they dissolve/disintegrate very fast when placed in the mouth. Immediate release

tablet are the most convenient dosage forms for dysphagic, geriatric patients with swallowing

problem. They do not require water for administration, thus are good alternative for travelers and for

bed ridden patients. They simply vanish when placed in the mouth, so cannot be hidden in mouth by

psychotic patients. Immediate release tablet are designed to disintegrate rapidly on contact with

saliva and enable oral administration without water or chewing these formulations offer increased

convenience and ease of administration with the potential to improve patient compliance particularly

in certain populations where swallowing of conventional solid oral dosage forms present difficulties.

United states food and Drug Administration (FDA) center for Drug Evaluation and Research

(CDER) define orally disintegrating tablets in the Orange Book as “A solid dosage form which

contain a medicinal substance or active ingredient which disintegrates rapidly within a matter of

second when placed upon a tongue” European Pharmacopoeia described orally disintegrating

tablets as “ uncoated tablets intended to be placed in the mouth where they disperse rapidly before

being swallowed and as tablets which should disintegrate within 3 min”.[4]

Figure 1. Conceptual diagram of FDT



Immediate release tablet are also called as Fast – dissolving tablets, Melt-in mouth tablets or

dispersible tablets, Rapimelts, Porous tablets, Quick dissolving etc. Fast dissolving tablets are those

when put on tongue disintegrate instanteously releasing the drug which dissolves or disperses in the

saliva. The Faster the drug into solution, quicker the absorption and onset of clinical effect some

drugs are absorbed are absorbed form the mouth pharynx and esophagus as the saliva passes down

into the stomach In Such cases bioavailability of drug is significantly greater than those observed

form conventional tablets dosage form.

DESIRED CRITERIA FOR IMMEDIATE RELEASE TABLET [5, 6]

Not require water to swallow, but it should dissolve or disintegrate in the mouth in matter of

seconds.

Be compatible with taste masking

Be portable without fragility concern.

Have a pleasant mouth feel.

Leave minimum or residue in the mouth after oral administration

Exhibit low sensitive to environmental condition as temperature and humidity.

Ease of administration to patients who refuse to swallow a tablet such as pediatric and geriatric

patients and psychiatric patients.

Convenience of administration and accurate dosing as compared to liquids.

Good mouth feels property of Immediate release tablets helps to change the basic view of

medication as “bitter pill” particularly for pediatric.

Rapid dissolution of drug and adsorption which may produce rapid onset of action.

Some drugs are absorbed form the month pharynx and oesophagus as the saliva passes down

into the stomach in such cases bioavailability of drugs is increased.

Pregastric absorption can resulting improved bioavailability and as a result of reduced dosage,

improved clinical performance though a reduction of unwanted effects.

ADVANTAGES OF IMMEDIATE RELEASE TABLET

1. Accurate Dosing: Being unit solid dosage Forms, Provide of accurate dosing easy portability

and manufacturing, good physical and chemical stability and an ideal alternative for pediatric

and geriatric patients.

2. Enhanced bioavailability : Bioavailability of drug is enhanced due to absorption form mouth

pharynx and esophagus.

3. Rapid action: Fast onset of therapeutic action as tablet gets disintegrated rapidly along with

quick dissolution and absorption in oral cavity.



4. Patient compliance: No need of water to swallow the dosage form. Hence it is convenient for

patients who are travelling and do not have immediate access to water.

5. Ease of Administration : Convenient to administer specially for geriatric pediatric mentally for

patients who are travelling and do not have immediate access to water

6. Obstruction Free: No Risk of suffocation in airways due to physical obstruction when

swallowed thus providing improved safety and compliance.

7. Enhanced palatability: Good mouth feels, especially for pediatric patients as taste masking

technique is used to avoid avoiding the taste of drug.

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

9. Business Avenue : Provide new business opportunities in the form of product differentiation,

line extension uniqueness and life cycle management

10. Cost Effective: Conventional processing and packaging equipment allow the manufacturing of

tablets at low cost.

LIMITATIONS OF IMMEDIATE RELEASE TABLETS

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

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

NEED FOR DEVELOPMENT OF IMMEDIATE RELEASE TABLET[9]

1. Patient factors:

Orally disintegrating dosage forms are particularly suitable for patients (particularly pediatric

and geriatric patients) who are not able to swallow traditional and capsules with an 8 – oz glass

of water.

2. Effectiveness factor:

Increased bioavailability and faster on set of action are major claim of these formulations.

Dispersion in saliva in oral cavity cause pregastric absorption form some formulations in the

those cases where drug dissolves quickly. Buccal pharyngeal and gastric regions are absorption

for many drugs. Any pregastric absorption avoids first pass metabolism and can be a great

advantage in drugs that undergo a great deal of hepatic metabolism.

3. Manufacturing and marketing factors:

Developing new drugs delivery technologies and utilizing them in product development is

critical for pharmaceutical industries to survive, regardless of their size. As a drug nears the end

of its patent life, it is common for pharmaceutical manufacturers to develop given drug entity in

a new and improved dosage form.



IDEAL CHARACTERISTIC OF IMMEDIATE RELEASE TABLET

Not require water to swallow but is should dissolve or disintegrate in the mouth in matter of

second.

Allow high drug loading and have acceptable taste masking property.

Be portable without fragility concerns and have a pleasing mouth feel.

Leave minimal or no residue in the mouth after oral administration.

Exhibit low sensitivity to environmental conditions as humidity and temperature.

Allow the manufacture of tablet using conventional processing and packaging equipment at low

cost.

Figure 2: Ideal Mouth dissolving tablet

TECHIQUES FOR FORMULATION OF IMMWEDIATE RELEASE TABLET

1. Freeze draying / Lyophilization

In freeze-drying process, the water is sublimed from the product after it is frozen. This technique

forms the basis of Zydis, Quicksolv and Lyoc technologies which are used to manufacture

MDTs. The process involves the following steps:

Stage 1 - Bulk preparation of an aqueous drug solution or suspension and its subsequent precise

dosing into pre-formed blisters. It is the blister that actually forms the tablet shape and is,

therefore, an integral component of the total product package.

Stage 2 - Passing the filled blisters through a specially designed cryogenic freezing process to

control the ultimate size of the ice crystals which ensures that the tablets possess a porous matrix

to facilitate the rapid disintegration property. These frozen units are then transferred to large-

scale freeze dryers for the sublimation process, where the majority of the remaining moisture is

removed from the tablets.

Stage 3 - Sealing the open blisters using a heat-seal process to ensure stability and protection of

the product from varying environmental conditions.

Excipients-

Polymers (e.g., gelatin, alginates and dextrin) to provide strength and rigidity to tablets;



Polysaccharides (e.g., mannitol and sorbitol) to impart crystallinity and hardness to the matrix

and to improve palatability;

Collapse protectants (e.g., glycine) to prevent the product from shrinking in its packaging

during manufacturing or storage;

Flocculating agents (e.g., xanthan gum and acacia) to provide uniform dispersion of drug

particles;

Preservatives (e.g. parabens) to prevent microbial growth;

Permeation enhancers (e.g. sodium lauryl sulfate) to improve transmucosal permeability

pH adjusters (e.g. citric acid etc.) to optimize chemical stability;

Flavors and Sweeteners to improve patient compliance and

Water to ensure formation of porous units.

Advantages: The major advantage of using this technique is that the tablets produced by this

technology have very low disintegration time and have great mouth feel due to fast melting effect.

Disadvantages: Although being a fairly routine process, lyophilization has some disadvantages

like it is a relatively expensive and time consuming process. Furthermore, the product obtained is

poorly stable and fragile, rendering conventional packaging unsuitable.

Lyophilization Technology. Patented technology based on this process is Zydis technology

2. Moulding

Moulded tablets invariably contain water-soluble ingredients due to which the tablets dissolve

completely and rapidly. Following are the different tablet moulding techniques:

i. Compression Molding:

This manufacturing process involves moistening the powder blend with a hydroalcoholic solvent

followed by pressing into mould plates to form a wetted mass (compression moulding). The

solvent is then removed by air drying, a process similar to the manufacture of tablet triturates.

Such tablets are less compact than compressed tablets and possess a porous structure that hastens

dissolution.



ii. Heat Molding:

Heat-moulding process involves setting the molten mass containing a dispersed drug. This

process uses agar solution as a binder and a blister packaging well as a mould to manufacture the

tablet. A suspension containing drug, agar and sugar is prepared followed by pouring the

suspension into the blister packaging well, solidifying the agar solution at room temperature to

form a jelly and finally drying at approximately 30 °C under vacuum.

iii. Molding by vacuum evaporation without lyophization:

This process involves pouring of the drug excipient mixture (in the form of a slurry or paste)

into a mould of desired dimension, freezing the mixture to form a solidified matrix and finally

subjecting it to vacuum drying at a temperature within the range of its collapse temperature and

equilibrium freezing temperature. This results in the formation of a partially collapsed matrix.

This method differs from the lyophilization technique, as in the former the evaporation of free

unbound solvent occurs from a solid through the liquid phase to a gas, under controlled

conditions, instead of the sublimation which takes place in the latter process.

3. Spray Drying

Tablets which are manufactured from the spray-dried powder have been reported to disintegrate

in less than 20 seconds in aqueous medium. The formulation contained bulking agent like

mannitol and lactose, a superdisintegrant like sodium starch glycolate and croscarmellose

sodium and acidic ingredient (citric acid) and/or alkaline ingredients (e.g. sodium bicarbonate).

This spray-dried powder, which compressed into tablets showed rapid disintegration and

enhanced dissolution. Maximum drug release and minimum disintegration time were observed

with Kollidon CL excipient base as compared to tablets prepared by direct compression,

showing the superiority of the spray dried excipient base technique over direct compression

technique.

4. Direct Compression Method:

Direct compression represents the simplest and most cost effective tablet manufacturing

technique. In this method, tablets are prepared directly by compression of the mixture of drug

and excipients without any preliminary treatment. The mixture which is to be compressed must

have good flow properties. This method complete within 3 steps:

a. Milling of drug and excipients

b. Mixing of drug and excipients

c. Tablet compression



Figure 3: Process of Direct Compression

Sr. No. Ideal requirements Advantages Limitations

1. Flowability Cost effective production Segregation

2. Compressibility Better stability of API Variation in functionality

3. Dilution Potential Faster dissolution Low dilution potential

4. Reworkability Less wear and tear of punches Reworkability

5. Stability Simple validation Poor compressibility of API

6. Controlled Particle Size Low microbial contamination Lubricant sensitivity

Table 1: Ideal Requirements, Advantages and Limitations of Direct Compression

This technique can now be applied to preparation of immediate release tablet because of improved

excipients especially superdisintegrants, effervescent agent, suger based excipients:

A. SUPER DISINTEGRANTS[12]

Disinntegrants are substances routinely included in tablet formulations and in some hard shell

capsule formulations to promote moisture penetration and dispersion of the matrix of dosage form

in dissolution fluids. An oral solid dosage form should ideally disperse into the primary particles

from which it was prepared. Superdisintegrants are generally used at a low concentration, typically

1-10% by weight relative to total weight of dosage unit. Generally employed superdisintegrants are

crosscarmellose sodium (Ac-Di-Sol), Crosspovidone (CP), sodium starch glycolate(SSG) etc.

which represent example of cross linked cellulose, crosslinked polymer and crosslinked starch

respectively.

SELECTION OF SUPER DISINTEGRANTS:

Although superdisintegrants primarily affect the rate of disintegration, but when used at high levels

they can also affect mouth feel, tablet hardness and friability. Hence, various ideal factors to be

considered while selecting an appropriate superdisintegrants for a particular formulation should:

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

Be compactable enough to produce less friable tablets.

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

compliance.

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

MECHANISM OF ACTION OF DISINTEGRANT:

1. Swelling

General mechanism of action for tablet disintegration which is most widely accepted is swelling.

Tablets with high porosity due to lack of adequate swelling force show poor disintegration.



Sufficient swelling force with low porosity is exerted in the tablet. If the packing fraction is very

high, fluid is unable to penetrate in the tablet & disintegration is again slows down.

Swelling (Particles swell and break up the matrix form within; swelling sets up; localized stress

spread through out the matrix).

2. Water wicking

Effective disintegrants that do not swell are believed to impart their disintegrating action through

porosity and capillary action. Tablet porosity provides pathways for the preparation of fluid into

tablets. The disintegrant particles themselves act to enhance porosity and provide pathways into the

tablet. Liquid is drawn up or “wicked” into these pathways through capillary action and rupture the

interparticulate bonds causing the tablet to break apart.

Porosity and capillary action (Wicking) [10]

(Disintegrant pull water into the pores and

reduces the physical bonding forces between the particles)

3. Particle repulsive forces

Another mechanism of disintegrating 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

Repulsion Theory: (Water is drawn into the pores and particles repel each other due to the

resulting electrical force).

4. Deformation (Elastic recovery)

Disintegranted particles get deformed, during tablets compression and when these deformed

particles come in contact with aqueous media or water they get into their normal structure.

Swelling capacity of starch was improved during compression. Due to this increase in size of the

deformed particles produces a break up of the tablet.

Elastic recovery

5. Due to release of gases

Carbon dioxide gets released within tablets on wetting due to interaction between bicarbonate and

carbonate with citric acid or tartaric acid. The tablet disintegrates due to generation of pressure

within the tablet. This effervescent mixture is used when pharmacist needs to formulate very rapidly

dissolving tablets or fast disintegrating tablet. As these disintegrants are highly sensitive to small



changes in humidity level and temperature, strict control of environment is required during

preparation of the tablets. The effervescent blend is either added immediately prior to compression

or can be added into two separate fractions of formulation.

6. By enzymatic reaction

Enzymes present in the body also act as disintegrants. These enzymes dearth the binding action of

binder and helps in disintegration. Due to swelling, pressure is exerted in the outer direction that

causes the tablet to burst or the accelerated absorption of water leads to an enormous increase in the

volume of granules to promote disintegration.

7. Because of heat of wetting (Air expansion)

When disintegrants with exothermic properties get wetted, localized stress is created due to capillary

air expansion, which aids in disintegration of tablet. This explanation, however, is limited to only a

few types of disintegrants and cannot describe the action of most modern disintegrating agents.

B. EFFERVESCENT AGENTS:

The evolution of CO2 as a disintegrating mechanism forms the basis of the patented Orasolv

technology and is frequently used to develop over-the-counter formulations. The product contains

microparticles and is slightly effervescent in nature. Saliva activates the effervescent agent which

causes the tablet to disintegrate.

C. SUGER BASED EXCIPIENTS:

This is another approach to manufacture ODT by direct compression. The use of sugar based

excipients especially bulking agent like dextrose, fructose, isomalt, lactilol, maltilol, maltose,

mannitol, sorbitol, starch hydrolysate, polydextrose and xylitol, which display high aqueous

solubility and sweetness, and hence impart taste masking property and a pleasing mouthfeel.

Mizumito et. al. have classified suger-based excipients into two types on the basis of molding and

dissolution rate.

Type 1 saccharides (Lactose, Mannitol): exhibit low mouldability but high dissolution rate.

Type 2 saccharides (Maltose, Maltilol): exhibit high mouldability and low dissolution rate.

5. Sublimation:

The slow dissolution of the compressed tablet containing even highly water soluble ingredients

is due to the low porosity of the tablets. Inert solid ingredients that volatilize readily (e.g. urea,

ammonium carbonate, ammonium bicarbonate, hexa methelene tetramine, camphor etc.) were

added to the other tablet ingredients and the mixture is compressed into tablets. The volatile

materials were then removed via sublimation, which generates porous structures. Additionally,

several solvents (e.g. cyclohexane, benzene) can be also used as pore forming agents,



Steps Involved in sublimation

6. Phase transition process

This processes for the disintegration of FDTs by phase transition of sugar alcohols using

erythritol (melting point 122°C), xylitol (93-95°C), trehalose (97°C), and mannitol (166°C).

Tablets were produced by compressing a powder containing two sugar alcohols with high and

low melting points and subsequent heating at a temperature between their melting points. Before

heating process, the tablets do not have sufficient hardness because of low compatibility. The

tablet hardness was increased after heating, due to the increase of inter particle bonds or the

bonding surface area in tablets induced by phase transition of lower melting point sugar alcohol.

7. Melt granulation

In this process, FDTs can be prepared by incorporating a hydrophilic waxy binder (super

polystate) like PEG-6-stearate. Super polystate is a waxy material with melting point of 33-37°C

and a hydrophilic- lipophilic balance of 9. It not only acts as a binder and increases the physical

resistance of tablets, but also helps in the disintegration of tablets as it melts in the mouth and

solubilizes rapidly leaving no residue. Super polystate was incorporated in the formulation of

FDTs by melt granulation method where granules are formed by the molten form of this

material.

8. Mass extrusion

In this method active blend is softened using the solvent mixture of water-soluble polyethylene

glycol and methanol and then subsequent expulsion of softened mass through the extruder or

syringe is made to get a cylinder of the product into even segments using heated blade to form

tablet. The dried cylinder can also be used to coat granules for bitter drugs and thereby achieve

taste masking.

9. Oral disintegrating Thin Films:

It is a new frontier in immediate release tablet that provides a very convenient means of taking

medications and supplements. In this technique, a non-aqueous solution is prepared containing

water soluble film forming polymer (pullulan, carboxy methylcellulose, hydroxypropyl



methylcellulose, hydroxyl ethylcellulose, hydroxyl propylcellulose, polyvinyl pyrrolidone,

polyvinyl alcohol or sodium alginate, etc.), drug and other taste masking ingredients, which is

allowed to form a film after evaporation of solvent. In case of a bitter drug, resin adsorbate or

coated microparticles of the drug can be incorporated into the film. This film, when placed in

mouth, melts or dissolves rapidly, releasing the drug in solution or suspension form. The

features of this system include paper thin films of size less than 2×2 inches, dissolution in 5 sec,

instant drug delivery and flavoured after taste.

10. Nanoionization

A recently developed Nanomelt technology involves reduction in the particle size of drug to

nano size by milling the drug using a proprietary wet-milling technique. The nanocrystals of the

drug are stabilized against agglomeration by surface adsorption on selected stabilizers, which are

then incorporated into MDTs. This technique is especially advantageous for poorly water

soluble drugs. Other advantages of this technology include fast disintegration/dissolution of

nanoparticles leading to increased absorption and hence higher bioavailability and reduction in

dose, cost effective manufacturing process, conventional packaging due to exceptional durability

and wide range of doses (up to 200mg drug per unit).

11. Cotton Candy process

The FLASHDOSE® is a IMMEDIATE RELEASE TABLET manufactured using Shearform™

technology in association with Ceform TI™ technology to eliminate the bitter taste of the

medicament. A matrix known as „floss‟, with a combination of excipients, either alone or with

drugs is prepared by using shear form technology. Like cotton-candy fibers floss is fibrous

material made of saccharides such as sucrose, dextrose, lactose and fructose at temperatures

ranging between 180–266 °F. However, other polysaccharides such as polymaltodextrins and

polydextrose can be transformed into fibers at 30–40% lower temperature than sucrose. Due to

this modification thermo labile drugs can be safely incorporated into the formulation. This

process results in a highly porous product and offer very pleasant mouth feel due to fast

solubilization of sugars in presence of saliva.

2.8 PATENTED TECHNOLOGIES FOR IMMEDIAT RELEASE TABLET

1. Zydis Technology (R.P.Scherer Inc.)

Zydis formulation is a unique freeze dried tablet in which drug is physically entrapped or

dissolved within the matrix of fast dissolving carrier material. When zydis units are put into the

mouth, the freeze-dried structure disintegrates instantaneously and does not require water to aid

swallowing. The zydis matrix is composed of many material designed to achieve a number of

objectives. To impart strength and resilience during handling,polymers such as gelatin, dextran

or alginates are incorporated. These form a glossy amorphous structure, which imparts strength.



2. Orasolv Technology (Cima Labs Inc.)

OraSolv is Cima's first fastdissolving/ disintegrating dosage form. The OraSolv technology,

unlike Zydis, disperses in the saliva with the aid of almost imperceptible effervescence. Orasolv

technology is an oral dosage form that combines tastemasked drug ingredients with an

effervescent excipient system and requires conventional manufacturing process and equipment.

The OraSolv technology is utilized in more than eight marketed products: four Triaminic

Softchew formulations, Tempra FirsTabs, and Remeron Soltab.

3. Durasolv Technology (Cima Labs Inc.)

Durasolv is the patented technology of CIMA labs. The tablets made by this technology consist

of drug, filler and a lubricant. Tablets are prepared by using conventional tableting equipment

and have good rigidity. These can be packaged into conventional packaging system like blisters.

Durasolv is an appropriate technology for product requiring low amount of active ingredients.

4. Lyoc Technology (Pharmalyoc Inc.)

Lyoc technology is patented by pharmalyoc. Oil in water emulsion is prepared and placed

directly into blister cavities followed by freeze-drying. Nonhomogeneity during freeze-drying is

avoided by incorporating inert filler to increase the viscosity finally the sedimentation. High

proportion of filler reduces porosity of tablets due to which disintegration is lowered.

5. Flashtab Technology (Ethypharm Inc.)

Prographarm laboratories have patented the Flash tab technology. Tablet prepared by this system

consists of an active ingredient in the form of micro crystals. Drug micro granules may be

prepared by using the conventional techniques like coacervation, micro encapsulation and

extrusion spheronisation. All the processing utilized conventional tabletting technology.

6. Flashdose Technology (Fuisz Technology Ltd.)

Flash dose technology has been patented by fuisz. Nurofen meltlet, a new form of ibuprofen as

melt in mouth tablets prepared using flash dose technology is the first commercial product

launched by Biovail Corporation. Flash dose tablets consist of self-binding shear form matrix

termed as “floss”. Shear form matrices are prepared by flash heat processing.

7. Wowtab Technology (Yamanouchi Pharma Technologies Inc.)

Wowtab technology was developed by Yamanouchi Pharma Technologies. “Wow” means

without water. The active ingredients may constitute upto 50% w/w of the tablet. Here,

saccharides of both low and high Moldability are used to prepare the granules. Moldability is the

capacity of a compound to be compressed. Highly Moldable substance has high compressibility

and thus slow dissolution. The combination of high and low Moldability is used to produce

tablets of adequate hardness & a rapidly melting strong tablet. Active ingredients are mixed with

low Moldability saccharides and then granulated with high Moldability saccharides and then



compressed into tablet. Wowtab product dissolves quickly in 15 s or less. Wowtab product can

be packed in both into conventional bottle and blister packs. This technology utilizes

conventional granulation and tableting methods and used for both water-soluble and insoluble

drugs. The manufacturing process involves granulating low moldable sugars (e.g. mannitol,

lactose, glucose, sucrose, and erythritol) that show quick dissolution characteristics with high

moldable sugars (e.g. maltose, maltitol, and sorbitol). The result is a mixture of excipients that

have fast-dissolving and high moldable characteristics.

8. Advatab Technology (Eurand International)

Advatab tablets disintegrate rapidly in the mouth, typically in less than 30 seconds, to allow for

convenient oral drug administration without water. These tablets are especially suited to those

patients that experience difficulty in swallowing capsules and tablets. AdvaTab is distinct from

other ODT technologies as it can be combined with Eurand‟s complimentary particle

technologies like its world leading Microcaps® tastemasking technology and its Diffucaps® ,

controlled release technology. The pairing of AdvaTab with Microcaps creates products that

offer the dual advantage of a patient preferred dosage form, together with a superior taste and

smooth mouth feel. This is a critical advantage as the unpleasant taste of drugs is a significant

restriction in the application of other ODT technologies.

9. Oraquick Technology (KV Pharmaceutical Co. Inc.)

The Oraquick fastdissolving/ disintegrating tablet formulation utilizes a patented taste masking

technology. The taste masking process does not utilize solvents of any kind, and therefore leads

to faster and more efficient production.Also, lower heat of production than alternative fast

dissolving/ disintegrating technologies makes Oraquick appropriate for heat- sensitive drugs.

Oraquick claims quick dissolution in a matter of seconds, with good tastemasking. There are no

products using the Oraquick technology currently on the market, but KV Pharmaceutical has

products in development such as analgesics, scheduled drugs, cough and cold, psychotropics,

and anti-infectives.

10. Quicksolv Technology (Janssen Pharmaceutics)

This technology is patented by Janssen Pharmaceuticals. It utilizes two solvents in formulating a

matrix, which disintegrates instantly. Methodology includes dissolving matrix components in

water and the solution or dispersion is frozen. Then dry the matrix by removing water using an

excess of alcohol (solvent extraction). Thus the product formed has uniform porosity and

adequate strength for handling.

11. Ziplets (Eurand International)

Recently Eurand (Pessano con Bornago, Italy) developed the Ziplets technology, which can be

used with water insoluble compounds as both bulk actives and as coated microparticles (the



latter containing soluble and/or insoluble drugs). Infact, tablets composed primarily of water-

soluble components often tend to dissolve rather than disintegrate, resulting in a much longer

disintegration time. As the soluble components dissolve on the tablets outer layer, the rate of the

water diffusion into the tablet core decreases because of the formation of concentrated viscous

solutions.

INGREDIENTS USED IN IMMEDIATE RELEASE TABLET:

Sr.No Ingredients Role Example

1. Superdisintegrants To promote the breakup of the tablets into

smaller fragments in an aqueous environment

there by increasing the available surface area

and promoting a more rapid release of drug.

Croscarmellose sodium,

Crospovidone, Carmellose,

Carmellose calcium, Sodium starch

glycolate ion exchange resins (e.g.

Indion 414) etc.

2. Binders These materials are added either dry or wet-

form to form granules or to form cohesive

compacts for directly compressed tablets

Cellulosic polymers, Povidones,

Polyvinyl alcohols(PVA), and

acrylic polymers. Acrylic polymers

used are the ammonium Ethacrylate

copolymer, Polyacrylate, and

Polymethacrylate etc.

3. Antistatic agent To reduce or eliminate build up of static

electricity

Colloidal silica(Aerosil),

precipitated silica

( Sylod.FP244), talc, maltodextrins,

beta cyclodexrin etc.

4. Lubricants

(glidants)

To prevent adhesion of the tablet materials to

the surface of dies and punches, reduce inter

particle friction and may improve the rate of

flow of the tablet granulation.

Magnesium stearate, Stearic acid,

Leucine, Sodium benzoate, Talc,

Magnesium lauryl sulphate, Liquid

paraffin, Zinc state, calcium state,

Polyethylene glycol etc.

5. Flavours To giving flavours.

To enhance the patient compliance.

Peppermint flavour, Clove oil,

Anise oil, Eucalyptus oil. Flavoring

agents include Vanilla, Citrus oils,

Fruit essences etc.

6. Sweeteners To masking the taste of drug. To enhance the

patient compliance.

Sorbitol, Mannitol, Maltitol

solution, Xylitol, Erythritol,

Sucrose, Fructose, Maltose,

Aspartame,Sugars derivatives etc.

7. Fillers(Diluent) To make required bulk of the tablet.

To improve cohesion and promote flow in

direct compression.

Directly compressible spray dried

Mannitol, Sorbitol, Xylitol, Calcium

carbonate, Magnesium carbonate,

Calcium phosphate, Pregelatinized

starch, Magnesium trisilicate,

Aluminium hydroxide etc.

8. Surface active

agent

(wetting agent)

To allow easy spreading of water on the

surface. It also makes water easy to displace

air and spread over the surface inside the

tablet.

Sodiumdodecylsulphate,

Sodiumlaurylsulfate, Tweens

(Sorbitan fatty acid esters) Spans

(Sorbitan fatty acid esters),

Polyoxyethylene stearate etc.

9. Colour To enhance the patient compliance Sunset yellow, Amaranth etc.



EVALUATION PARAMETER FOR IMMEDIATE RELEASE TABLET

PRECOMPPRESION:

Bulk Density:

Apparent bulk density was determine by pouring the 5 gram of powder into a 100 ml granulated

cylinder. The bulk volume (V) poured drug was determined. The bulk density was calculated using

the formula.

V = Vb - Vp

ρb = M / Vb

Where : ρb - bulk density

M- is the weight of powder

V- is the volume of powder

Tapped Density:

Weight 5 g. of powder and placed in a measuring cylinder. Measuring cylinder containing known

mass (5 gm) of powder was tapped for 100 times or fixed time. The minimum volume (Vt)

occupied was measured. The tapped density was calculated using following formula.

ρt = M / Vt

Compressibility Index:

The simplest way for measurement of free flow of powder is compressibility, a indication of the

ease with which a material can be induced to flow is given by Compressibility Index. The value

below 15% indicates a powder with give rice to good flow properties, whereas above 25% indicate

poor flowability. Which is calculated follows.

% C.I. = ρt - ρb ρt/ ˟ 100

Hausner ratio:

Hausner ratio is an indirect index of ease of powder flow. Hosner ratio is the ratio of tapped density

to bulk density. Lower the value of Housner ratio better is the flow property. Powder with Housner

ratio less than 1.18, 1.19, 1.25, 1.3- 1.5 and greater the 1.5 indicate excellent, good, passable, and

very poor, respectively. It is calculated by following formula.

Hausner ratio = ρt / ρt

Voide Volume:

Voide volume (V) was obtained by difference between bulk volume(Vb) and tapped volume

(Vp).Voide volume can be calculated by following formula.

Angle of repose:

The angle of repose was determined using funnel method. Funnel that can be fit vertically with

stand at 6.3 cm. height. The opening end of funnel are closed with thumb until drug are poured. The

5 gm of powder was poured into funnel that can be raised vertically until a maximum cone hight (h)



was obtained. Radius of the heap (r) was measured and the angle of repose (ϴ) was calculated

using the formula.

Tan Ɵ = h/r

AFTER COMPREESION:

Thickness:

Tablet thickness can be measured using a simple procedure. 5 tablets were taken and their thickness

was measured using Vernier calipers.

Hardness:

It is the force required to break a tablet by compression in the radial direction, it is an important

parameter in formulation of mouth dissolve tablets because excessive crushing strength

significantly reduces the disintegration time.In the present study the crushing strength of the tablet

was measured us-ing Pfizer hardness testers. An average of three observations is reported.

Uniformity of weight:

I.P. procedure for uniformity of weight was followed, twenty tablets were taken and their weight

was determined individually and collectively on a digital weighing balance. The average weight of

one tablet was determined from the collective weight. The weight variation test would be a

satisfactory method of determining the drug content uniformity.

Average weight of tablet % Deviation

80 mg or less ±10

More than 80 mg but less than 250 mg ±7.5

250 mg or more ±5

Assay:

Twenty tablets from each batch were weighed accurately and powdered powder equivalent to

100mg drug was shaken with 100 ml of 0.1N Hydrochloric acid in 100 ml amber colored

volumetric flask and from this 10 ml was pipette out and then dilute up to 100 ml. From standard

solution again 10 ml pipette out and diluted up to 100 ml in ml.

Disintegration time:

The test was carried out on 6 tablets using the apparatus specified in I.P.-1996 distilled water at

37ºC ± 2ºC was used as a disintegration media and the time in second taken for complete

disintegration of the tablet with no palatable mass remaining in the apparatus was measured in

seconds.

In-vitro drug release:

The development of dissolution methods for ODTs is comparable to the approach taken for

conventional tablets, and is practically identical. Dissolution conditions for drugs listed in a

pharmacopoeia monograph, is a good place to start with scouting runs for a bioequivalent ODT.

Other media such as 0.1N HCl and buffers (pH - 4.5 and 6.8) should be evaluated for ODT much in



the same way as their ordinary tablet counter parts. The USP 2 Paddle apparatus is used for this

purpose which is the most suitable and common choice for orally-disintegrating tablets, with a

paddle speed of 50 rpm commonly used. Typically the dissolution of ODT is very fast when using

USP monograph conditions; hence slower paddle speeds may be utilized to obtain a profile. The

USP 1 Basket apparatus may have certain applications but sometimes tablet fragments or

disintegrated tablet masses may become trapped on the inside top of the basket at the spindle where

little or no effective stirring occurs, yielding irreproducible dissolution profiles.

Friability test:

Friability of the tablets was determined using Roche friability (Electrolab, Mumbai). This device

subjects the tablets to the combined effect of abrasions and shock in a plastic chamber revolving at

25 rpm and dropping the tablets at a height of 6 inches in each revolution. Preweighed sample of

tablets was placed in the friabilator and were subjected to 100 revolutions. Tablets were de dusted

using a soft muslin cloth and reweighed. The friability (f) is given by the formula.

f = (1- W0 / W) × 100

Where, W0 = weight of the tablets before the test

W = the weight of the tablet after the test.

In-vitro dispersion time test:

To determine dispersion time 10 ml measuring cylinder was taken in which 6 ml distilled water was

added and tablet was dropped in it. Time required for complete dispersion was determined.

Wetting time:

Five circular tissue papers of 10 cm diameter are placed in a petridish with a 10 cm diameter. Ten

millimeters of water-containing Eosin, a water- soluble dye, is added to petridish. A tablet is

carefully placed on the surface of the tissue paper. The time required for water to reach upper

surface of the tablet is noted as a wetting time.

Water absorption ratio:

A piece of tissue paper folded twice was placed in a small Petri dish containing 6 ml of water. A

tablet was put on the paper & the time required for complete wetting was measured. The wetted

tablet was then weighed. Water absorption ratio (R), was determined using following equation

R = 10 ( Wa /Wb)

Where, Wb = weight of tablet before water absorption

Wa = weight of tablet after water absorption.

Accelerated Stability study:

The Orally disintegrating tablets are packed in suitable packaging and stored under the following

conditions for a period as prescribed by ICH guidelines for accelerated studies. (i) 40 ± 1 °C (ii) 50

± 1°c (iii) 37 ±1 ° C and Relative Humidity= 75% ± 5% The tablets were withdrawn after a period



of 15 days and analyzed for physical characterization (Visual defects, Hardness, Friability,

Disintegrations, and Dissolution etc.) and drug content. The data obtained is fitted into first order

equations to determine the kinetics of degradation. Accelerated stability data are plotting according

Arrhenius equation to determine the shelf life at 25 ° C.

Packaging:

Packaging special care is required during manufacturing and storage to protect the dosage of other

fast-dissolving dosage forms. Quick- dispersing and/or dissolving oral delivery systems, the system

can be packaged using various options, such as single pouch, blister card with multiple units,

multiple unit dispenser, and continuous roll dispenser, depending on the application and marketing

objectives.

Marketed Fast Dissolving Tablets in India:

TRADE NAME ACTIVE DRUG MANUFACTURER

Cefadur DT Cefadroxil Cipla (protec)

Cefinar DT Cefixime Zydus Alidac

Zofran ODT; Vomokind MD Ondansetron Glaxo wellcome; Mankind

Torrox MT; Dolib MD Rofecoxib Torrent Pharmaceuticals; panacea

Acivir DT Acyclovir Cipla

Dom DT; Domestal DT Domperidone Dr. Morepen; Torrent Pharma

Mosid MT Mosapride Torrent Pharma

Allegra ODT Fexofenadine Sanofi Aventis

Pepcid RPD Famotidine Merck & Co.

Maxalt- MLT Rizatriptan Merck & Co.

Mirtazapine ODT Mirtazapine Teva Pharmaceuticals

Zotacet MD Cetrizine HCl Zota Pharma

Romilast Montelukast Ranbaxy

Benadryl Allergy Fast Melt Diphenhydramine Pfizer Consumer Healthcare

CONCLUSION

The FDTs have potential advantages over conventional dosage forms, with their improved patient

compliance, convenience, bioavailability and rapid onset of action had drawn the attention of many

manufactures over a decade. FDTs formulations obtained by some of these technologies have

sufficient mechanical strength, quick disintegration/dissolution in the mouth without water.

These FDTs can be used easily in children who have lost their primary teeth and in geriatric

patients who have lost their teeth permanently. They remain solid during storage, which aid in

stability of dosage forms and transform into liquid form within few seconds after its

administration. As they have significant advantages as both solid and liquid dosage forms, FDTs

may be developed for most of the available drugs in near future. Mouth dissolving tablets can

offer several biopharmaceutical advantages such as improved efficiency over conventional

dosage forms. For example, they require smaller amounts of active ingredient to be effective,

improve absorption profiles, and offer better drug bioavailability than regular tablets and capsules.



REFERENCES:

1. Goyal R, Pathak A, Tiwari G, Shivhare R, Baghel SS, Sharma k, A review article on

formulation and evaluation of orodispersible tablets. World J. Pharm. Res. 2012, 1(3), 576-

590.

2. Ray C, Sharma V, Arora V, Fast dissolving tablets- A novel drug delivery system for

pediatric & geriatric patient. Int. Bulletin Drug Res., 1(2), 55-70.

3. Shinde SK, Banerjee SK, Grampurohit ND, Gaikwad DD, Gadhave MV, Sabale KS, An

overview of mouth dissolving technology. Deccan Pharma. J. Series. 2011, 2(2), 36-46.

4. Kumar A, Bhushan V, Singh M, Chauhan A, A review on evaluation and formulation of fast

dissolving tablets. Int. J. Drug Res. Tech., 2011, 1(1), 8-16.

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delivery. Asian J. Pharm. Sci. Res., 2012, 2(8), 13-21.

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Pharm. Res. 2009, 8(2), 161-172.

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93 | P a g e International Standard Serial Number (ISSN ...ijupbs.com/Uploads/8. RPA1415111015.pdf · This segment of formulation is especially dosing for dysphagic, geriatric, pediatric