TSS 5

World Journal of Pharmaceutical Research
Singh et al. World Journal of Pharmaceutical Research

SJIF Impact Factor 5.045
Volume 3, Issue 7, 755-791. Review Article ISSN 2277 7105
A REVIEW ON MOUTH DISSOLVING TABLET USING DIFFERENT

SUPER DISINTEGRANT
Mr. Vijay Kumar Singh*1, Utkarsh Singh1, Ashutosh Mishra2, Dinesh Chandra1,
Rajesh Sahu1
Kamla Nehru Institute of Management And Technology, Faridipur, Sultanpur.

A N D College of Pharmacy, Babhnan, Gonda.
Article Received on
ABSTRACT
13 July 2014, Historically, the oral route of drug administration has been the
Revised on 07 August 2014, one used most for both conventional as well as novel drug
Accepted on 02 Sept 2014
delivery. The reasons for this preference are obvious because of
the ease of administration and widespread acceptance by
*Correspondence for patients. Drugs taken orally for systemic effects have variable
Author
absorption rates and variable serum concentrations which may be
Vijay Kumar Singh
unpredictable. This has led to the development of sustained release
Kamla Nehru Institute of
Management And Technology, and controlled-release systems. The high acid content and ubiquitous
Faridipur, Sultanpur. A N D digestive enzymes of the digestive tract can degrade some drugs well
College of Pharmacy, Babhnan, before they reach the site of absorption into the bloodstream. This
Gonda.
is a particular problem for ingested proteins. Therefore, this
route has limitations for administration of biotechnology products.
Many macromolecules and polar compounds cannot effectively traverse the cells of the
epithelial membrane in the small intestines to reach the bloodstream. Their use is limited
to local effect in the gastrointestinal tract. Many drugs become insoluble at the low pH levels
encountered in the digestive tract. Since only the soluble form of the drug can be absorbed
into the bloodstream, the transition of the drug to the insoluble form can significantly reduce
bioavailability. The drug may be inactivated in the liver on its way to the systemic
circulation. An example of this is the inactivation of glyceryltrinitrate by hepatic
monoxygenase enzymes during the first pass metabolism. Some drugs irritate the
gastrointestinal tract and this is partially counteracted by coating. Oral route may not be
suitable for drugs targeted to specific organs. Despite disadvantages, the oral route remains
the preferred route of drug delivery. Several improvements have taken place in the
www.wjpr.net Vol 3, Issue 7, 2014. 755

formulation of drugs for oral delivery for improving their action.
Keyword: Mouth Dissolving Tablet, Synthetic Superdisintegrants, Natural

Superdisintegrants.
INTRODUCTION
1.1 Drug Delivery Systems [Jain kewal k. ,2007]

A drug delivery system (DDS) is defined as a formulation or a device that enables
the Introduction of a therapeutic substance in the body and improves its efficacy and
safety by controlling the rate, time, and place of release of drugs in the body. This process
includes the administration of the therapeutic product, the release of the active ingredients
by the product, and the subsequent transport of the active ingredients across the biological
membranes to the site of action. The term therapeutic substance also applies to an agent
such as gene therapy that will induce in vivo production of the active therapeutic agent.
Gene therapy can fit in the basic and broad definition of a drug delivery system. Gene
vectors may need to be introduced into the human body by novel delivery methods.
However, gene therapy has its own special regulatory control. Drug delivery system is an
interface between the patient and the drug. It may be a formulation of the drug to
administer it for a therapeutic purpose or a device used to deliver the drug. This distinction
between the drug and the device is important, as it is the criterion for regulatory control
of the delivery system by the drug or medicine control agency. If a device is introduced
into the human body for purposes other than drug administration, such as therapeutic
effect by a physical modality or a drug may be incorporated into the device for preventing
complications resulting from the device, it is regulated strictly as a device. There is a
wide spectrum between drugs and devices, and the allocation to one or the other category
is decided on a case by case basis.
1.1.1 Drug Delivery Routes [Jain kewal k. ,2007]

Drugs may be introduced into the human body by various anatomical routes. They may
be intended for systemic effects or targeted to various organs and diseases. The choice of
the route of administration depends on the disease, the effect desired, and the product
available. Drugs may be administered directly to the organ affected by disease or given
systemically and targeted to the diseased organ. A classification of various methods of
systemic drug delivery by anatomical routes is shown:

A classification of various anatomical routes for systemic drug delivery

1. Gastrointestinal system Oral Rectal
2. Parenteral Subcutaneous injection Intramuscular injection Intravenous injection Intra-
arterial injection
3. Transmucosal: buccal and through mucosa lining the rest of gastrointestinal tract
4. Transnasal
5. Pulmonary: drug delivery by inhalation
6. Transdermal drug delivery
7. Intra-osseous infusion
Oral Drug Delivery [Jain kewal k. ,2007]

Historically, the oral route of drug administration has been the one used most for
both conventional as well as novel drug delivery. The reasons for this preference are
obvious because of the ease of administration and widespread acceptance by
patients. Major limitations of oral route of drug administration are as follows:
1. Drugs taken orally for systemic effects have variable absorption rates and variable
serum concentrations which may be unpredictable. This has led to the development
of sustained release and controlled-release systems.
2. The high acid content and ubiquitous digestive enzymes of the digestive tract can
degrade some drugs well before they reach the site of absorption into the
bloodstream. This is a particular problem for ingested proteins. Therefore, this
route has limitations for administration of biotechnology products.
3. Many macromolecules and polar compounds cannot effectively traverse the cells of
the epithelial membrane in the small intestines to reach the bloodstream. Their use is
limited to local effect in the gastrointestinal tract.
4. Many drugs become insoluble at the low pH levels encountered in the digestive tract.
Since only the soluble form of the drug can be absorbed into the bloodstream, the
transition of the drug to the insoluble form can significantly reduce bioavailability.
5. The drug may be inactivated in the liver on its way to the systemic circulation. An
example of this is the inactivation of glyceryltrinitrate by hepatic monoxygenase
enzymes during the first pass metabolism.
6. Some drugs irritate the gastrointestinal tract and this is partially counteracted by coating.

7. Oral route may not be suitable for drugs targeted to specific organs.
8. Despite disadvantages, the oral route remains the preferred route of drug delivery.
Several improvements have taken place in the formulation of drugs for oral delivery
for improving their action.
1.2 Tablet
A tablet is a pharmaceutical dosage form. It comprises a mixture of active substances
and excipients, usually in powder form, pressed or compacted from a powder into a solid
dose. The excipients can include diluents, binders or granulating agents, glidants (flow
aids) and lubricants to ensure efficient tabletting; disintegrants to promote tablet
break-up in the digestive tract; sweeteners or flavors to enhance taste; and pigments to
make the tablets visually attractive. A polymer coating is often applied to make the tablet
smoother and easier to swallow, to control the release rate of the active ingredient, to make
it more resistant to the environment (extending its shelf life), or to enhance the tablet's
appearance. [Aulton M. E. 2, 2009]
Tablets are popular for several reasons:

1. The oral route represents a convenient and safe way of drug administration.
2. Compared to liquid dosage forms tablets have general advantages in terms of the
chemical and physical stability of the dosage form.
3. The preparation procedure enables accurate dosing of the drug.
4. Tablets are convenient to handle and can be prepared in a versatile way with respect to
their use and to the delivery of the drug.
1.2.1 Classification Of Tablets: [Aulton M. E. 2 , 2009]

Based on their drug-release characteristics, tablets can be classified into following types:
Disintegrating Tablets
The most common type of tablet is intended to be swallowed and to release the drug in
a relatively short time thereafter by disintegration and dissolution, i.e. the goal of
the formulation is fast and complete drug release in vivo. Such tablets are often referred
to as conventional or plain tablets. A disintegrating tablet includes normally at least the
following type of excipients: filler (if the dose of the drug is low), disintegrant, binder,
glidant, lubricant and antiadherent. As discussed above, the drug is released from a

disintegrating tablet in a sequence of processes, including tablet disintegration, drug

dissolution and drug absorption. All these processes will affect, and can be rate-
limiting steps for, the rate of drug bioavailability. The rate of the processes is
affected by both formulation factors and production conditions. The disintegration time
of the tablet can be markedly affected by the choice of excipients, especially disintegrant.
The type of filler and lubricant can also be of significant importance for tablet
disintegration.
Chewable Tablets
Chewable tablets are chewed and thus mechanically disintegrated in the mouth. The drug
is, however, normally not dissolved in the mouth but swallowed and dissolves in the
stomach or intestine. Thus, chewable tablets are used primarily to accomplish a quick
and complete disintegration of the tablet and hence obtain a rapid drug effect - or to
facilitate the intake of the tablet. A common example of the former is antacid tablets. In the
latter case, the elderly and children in particular have difficulty in swallowing tablets, and
so chewable tablets are attractive forms of medication. Important examples are vitamin
tablets. Another general advantage of a chewable tablet is that this type of medication can
be taken when water is not available. Chewable tablets are similar in composition to
conventional tablets except that a disintegrant is normally not included in the composition.
Flavouring and colouring agents are common, and sorbitol and mannitol are common
examples of fillers.
Effervescent Tablets
Effervescent tablets are dropped into a glass of water before administration, during
which carbon dioxide is liberated. This facilitates tablet disintegration and drug
dissolution; the dissolution of the tablet should be complete within a few minutes. As
mentioned above, the effervescent carbon dioxide is created by a reaction in water
between a carbonate or bicarbonate and a weak acid such as citric or tartaric. The amount
of sodium bicarbonate in an effervescent tablet is often quite high (about 1 g). After
dissolution of such a tablet, a buffered water solution will be obtained which normally
temporarily increases the pH of the stomach. The result is a rapid emptying of the
stomach and the residence time of the drug in the stomach will thus be short. As drugs
than in the stomach, effervescent tablets can thus show a fast drug bioavailability, which
can be advantageous, for example, for analgesic drugs. Another aspect of the short

residence time of the drug in the stomach is that drug-induced gastric irritation can be
avoided, e.g. for aspirin tablets, as the absorption of aspirin in the stomach can cause
irritation. Effervescent tablets also often include a flavor and a colourant. A water-soluble
lubricant is preferable in order to avoid a film of a hydrophobic lubricant on the surface of
the water after tablet dissolution. A binder is normally not included in the
composition.
Lozenges
Lozenges are tablets that dissolve slowly in the mouth and so release the drug dissolved in
the saliva. Lozenges are used for local medication in the mouth or throat, e.g. with
local anaesthesia, antiseptic and antibiotic drugs. They can thus be described as slow release
tablets for local drug treatment. Disintegrants are not used in the formulation, but
otherwise such tablets are similar in composition to conventional tablets. In addition,
lozenges are often coloured and include a flavour. The choice of filler and binder is of
particular importance in the formulation of lozenges, as these excipients should contribute to
a pleasant taste or feeling during tablet dissolution. The filler and binder should therefore
be water soluble and have a good taste. Common examples of fillers are glucose, sorbitol
and mannitol. A common binder in lozenges is gelatin. Lozenges are normally prepared
by compaction at high applied pressures in order to obtain a tablet of high mechanical
strength and low porosity which can dissolve slowly in the mouth.
Sublingual and Buccal Tablets

Sublingual and buccal tablets are used for drug release in the mouth followed by
systemic uptake of the drug. A rapid systemic drug effect can thus be obtained without
first-pass liver metabolism. Sublingual tablets are placed under the tongue and buccal tablets
are placed in the side of the cheek. Sublingual and buccal tablets are often small and
porous, the latter facilitating fast disintegration and drug release.
Extended-Release Tablets
In recent years there has been great interest in the development and use of tablets
which should be swallowed and thereafter slowly release the drug in the gastrointestinal
tract. Such tablets are denominated in various ways, such as slow release, prolonged
release, sustained release and extended-release. In the European Pharmacopoeia the term
extended-release has been chosen as denominator for these types of tablets and so is used
here. Extended-release tablets are often referred to as controlled-release preparations. This

latter term is somewhat misleading, as all tablets, irrespective of their formulation and use,
should release the drug in a controlled and reproducible way. An extended-release tablet
contains one dose of the drug which is released for a period of about 12-24 hours.
1.3 Mouth Dissolving Tablets

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 neuroleptics, cardiovascular agents, analgesics, anti-allergics
and drugs for erectile dysfunction. For these reason, tablets that can rapidly dissolve or
disintegrate in the oral cavity have attracted a great deal of attention. Orodispersible tablets
are not only indicated for people who have swallowing difficulties, but also are ideal for
active people.[Arjun G. et al, 2010]
Fast dissolving tablets are those when put on tongue disintegrate instantaneously releasing
the drug which dissolve or disperses in the saliva. Some drugs are absorbed from 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 from
conventional tablets dosage form. This is an innovative tablet technology where the dosage
form containing active pharmaceutical ingredients disintegrates rapidly, usually in a matter
of seconds, without the need for water, providing optimal convenience to the patient.
Innovators and inventor companies have given these tablets various names such as orally
disintegrating tablets (ODT), mouth dissolving (MD), fast melting, fast dissolving or
Orodisperse. The FDT is also known as fast melting, fast dispersing, rapid dissolve,rapid
melt, and/or quick disintegrating tablet. All FDTs approved by the Food and Drug
Administration (FDA) are classified as orally disintegrating tablets. Recently, the
European Pharmacopeia adopted the Term orodispersible tablet for a tablet that disperses
or disintegrates in less than 3 minutes in the mouth before swallowing. Such a tablet
disintegrates into smaller granules or melts in the mouth from a hard solid to a gellike
structure, allowing easy swallowing by patients. The disintegration time for good FDTs

varies from several seconds to about a minute. [Biradar S.S.et al. , 2006] , [Fu Yourong
et al , 2004]
1.3.1 Mechanism Of Absorption Of Drug Through Mouth:[SiddiquiNehalet al, 2011]

The delivery system is simply placed on a patients tongue or any oromucosal tissue.
Instantly wet by saliva due to presence of hydrophilic polymer and other excipients, the
film rapidly and dissolves to release the medication for oromucosal absorption.
Epithelium
LaminaPropria
submucosa
FIG 1.1: Different Layers of Oral Mucosa

1.3.2 Difficulties with Existing Oral Dosage Form [Panigrahi R Et El, 2010]
1. Patient may suffer from tremors therefore they have difficulty to take powder
andliquids.
2. In dysphasia physical obstacles and adherence to an esophagus may
causegastrointestinal ulceration.
3. Swallowing of solid dosage forms like tablet and capsules produce difficulty for
youngadult due to incomplete development of muscular and nervous system.
4. Liquid medicaments (suspension and emulsion) are packed in multidose
container;therefore achievement of uniformity in the content of each dose may be
difficult.
5. Buccal and sublingual formulation may cause irritation to oral mucosa, so
patientsrefused to use such medications.
6. Cost of products is main factor as parenteral formulations are most costly
anddiscomfort.
1.3.3 Requirements of Fast Disintegrating Systems [Sahoo S Et Al, 2010],[Siddiqui MN

Et Al, 2010]
1. No or little requirement of water to swallow, but it should dissolve or disintegrate in
the mouth in a matter of seconds.
2. Leave minimum or no residue in the mouth after oral administration.
3. Exhibit low sensitive to environmental condition as temperature and humidity.
4. Allow the manufacture of the tablet using conventional processing and packaging
equipments at low cost.
5. Ease of administration to the patient who cannot swallow, such as the elderly stroke
6. victims, bedridden patients, patient affected by renal failure and patient who refuse to
swallow such as pediatric, geriatric and psychiatric patients.
7. Rapid dissolution and absorption of the drug, which will produce quick onset of action.
8. Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes
down into the stomach. In such cases bioavailability of drug is increased
1.3.4 Advantage of Fast Dissolving Tablets [Reddy LH Et Al, 2002]

1. Convenience of administration and accurate dosing as compared to liquids.
2. No need of water to swallow the dosage form, which is highly convenient especially

for patients who are traveling and do not have immediate access to water.
3. Good mouth feel property helps to change the perception of medication as bitter pill
particularly in pediatric patient.
4. Pregastric absorption can result in improved bioavailability and as a result of reduced
dosage; improve clinical performance through a reduction of unwanted effects.
5. Good mouth feel property of these tablets helps to change the basic view of medication
as bitter pill, particularly for pediatric patients.
6. Rapid dissolution and absorption of drug, which may produce quick onset of action.
7. An increased bioavailability, particularly in cases of insoluble and hydrophobic drugs,
due to rapid disintegration and dissolution of tablets.
8. Ability to provide advantages of liquid medication in the form of solid form.
9. Stability for longer duration of time, since the drug remains in solid dosage form till it
is consumed. So, it combines advantage of solid dosage form in terms of stability and
liquid dosage form in terms of bioavailability.
FIG 1.2 : Advantages of MDT
1.3.5 Limitations of Fast Disintegrating Tablets[Bhowmik D Et Al, 2009],[Shaikh S Et

Al, 2010]
1. The tablets may leave unpleasant taste or grittiness in mouth if not formulated
properly.
2. The tablets usually have low hardness. So, they are friable and/or brittle and are
difficult to handle. They often require specialized peel-off blister packaging and
careful handling required.
3. Delivery of drug from the fast dissolving formulation would not expected to avoid first

pass metabolism since the unit disintegration rapidly and the drug would be
swallowed.
4. Drugs with relatively larger doses are difficult to formulate in to MDTs e.g
ciprofloxacin with adult dose containing 500 mg of the drug.
5. Patients who concurrently take anticholinergic medication may not be the best
candidates for MDTs and patients like Jorgens syndrome or dryness of the mouth due to
decrease saliva production may not be good candidates for these tablet formulation.
1.3.6 Overview of Oral Cavity[Toratoragorahowski, 2001]

Oral cavity is that area of mouth delineated by the lips, cheeks, hard palate, soft palate
and floor of mouth. The oral cavity consists of two regions.
1. Outer oral vestibule, which is bounded by cheeks, lips, teeth and gingiva (gums).
2. Oral cavity proper, which extends from teeth and gums with the roof comprising the
hard and soft palate. The tongue projects from the floor of the cavity.
FIG-1.3 Structure of Oral Cavity

The drug administered via the oral mucosa gain access to the systemic circulation through
a network of arteries and capillaries. The major artery supplying the blood to theoral cavity
is the external carotid artery. The venous backflow goes through branches of capillaries
and veins and finally taken up by the jugular vein.

1.3.7 Desired Characteristics & Development Challenges Of FDTs: [Prakashv Et Al,

2011]
Fast Disintegration
In a fast-dissolving drug delivery system the tablet is either dissolves or disintegrates
quickly in the oral cavity upon the contact with saliva within seconds, resulting in
solution or suspension of the administered medicine. Thus formed suspension is easy to
swallow.
Drug Properties
The drug properties should not significantly affect the tablet property. Many drug
properties could potentially affect the performance of FDTs. For example, the
solubility, crystal morphology, particle size, hygroscopicity, compressibility, and bulk
density of a drug can significantly affect the final tablet's characteristics, such as tablet
strength and disintegration. The FDT technology should be versatile enough to
accommodate unique properties of each drug. The drugs belonging to Biopharmaceutical
Classification System (BCS) Class II, i.e., the drugs with poor solubility and high
permeability are best suitable moieties for FDTs in a dose of 125 and 250 mg.
Tablet Strength and Porosity

Many attempts for fast-disintegrating behavior have been made by lyophilizing or
molding techniques and compressing wet powders to construct highly porous structure.
When the FDT is orally applied, the drug substance has to be dissolved so that it can be
absorbed. Dissolution process consists of various processes, e.g., wetting, disintegration,
and dissolution. FDTs which generally contains several excipients are involved in a
complex series of dissolution process that begins when the solvent contacts the solid and
penetrates the tablet matrix. Effect of excipients is assumed to be related to the surface
properties of the particles and solid matrix structure.The fabrication of lyophilized FDTs is
based on creating a porous matrix by subliming the water from pre-frozen aqueous
formulation of the drug containing matrix-forming agents and other excipients such as
lyoprotectants, preservatives, and flavors.
Moisture Sensitivity
Hygroscopicity is an important characteristic of a powder. For a soluble compound
the hygroscopicity is related to its solubility. FDTs should have low sensitivity to humidity.

This problem can be especially challenging because many highly water-soluble excipients
are used in formulation to enhance fast-dissolving properties as well as to create good
mouth feel. Those highly water-soluble excipients are susceptible to moisture; some will
even deliquesce at high humidity. A good package design or other strategy should be
developed to protect FDTs from adverse environmental conditions.
Taste of Active Ingredients

Taste is an important parameter in administering drugs orally. Undesirable taste is one of
the important formulation problems that are encountered with many drugs.
Administration of bitter drugs orally with acceptable level of palatability is a key issue for
healthcare providers. Taste masking of the drug may be achieved with preventing the
exposure of drug to the tongue through processing or adding competing taste-masking agents.
Exposure of solubilized drug to the oral cavity can be prevented by encapsulation in polymer
system or complexation.
Taste-masking technologies are increasingly focused on aggressively bitter-tasting drugs

like the macrolide antibiotics, non-steroidal anti-inflammatory drugs, and penicillins.
Taste masking of water-soluble bitter drugs, especially those with a high dose, is difficult
to achieve by using sweeteners alone. As a consequence, more efficient techniques such
as coating, microencapsulation, and granulation have been used in combination with
the sweeteners.
1.4Super disintegrants[Pahwa R Et Al, 2010]

Disintegrants 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 croscarmellose sodium (Ac-Di-Sol),
crospovidone (CP), sodium starch glycolate (SSG) etc. which represent example of cross-
linked cellulose, cross-linked povidone and cross-linked starch respectively.
Selection of appropriate formulation excipients and manufacturing technology is necessary
for obtaining the optimized design features of orally disintegrating dosage forms. Ideally,
superdisintegrants should c et al, 2011ause the tablet to disrupt, not only into the granules

from which it was compressed but also into powder particles from which the granules were
prepared.
FIG 1.4: Mechanism of Tablet Disintegration
1.4.1 Selection of Super disintegrants[Pahwar Et Al, 2010]

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 are:
1. Produce rapid disintegration, when tablet comes in contact with saliva in the
mouth/oral cavity.
2. Compactable enough to produce less friable tablets.
3. Produce good mouth feel to the patients. Thus, small particle size is preferred to
achieve patient compliance.
4. Particle size and Flow properties of the superdisintegrant.
5. Have good flow, since it improves the flow characteristics of total blend.
1.4.2 Method of Incorporation of Super disintegrants[Mangal M Et Al, 2012]

The incorporation of superdisintegrants in the dosage forms are mainly of three types:
1. Intra-granular or during granulation - In this process the superdisintegrants are blend
with other powders and granulation is carried out. Thus the superdisintegrants are
incorporated within the granules.
2. Extra-granular or prior to compression - In this process, the superdisintegrants are
mixed with prepared granules before compression.
3. Incorporation of superdisintegrants at intra and extra granulation steps- In this process

part of superdisintegrants are added to intra-granular and a part to extra- granules. This
method usually produces better results and more complete disintegration than type I
and type- II
1.4.3 Types of Superdisintegrants[Shah R Et Al, 2013]

The Superdisintegrants can be classified into two categories on the basis of their availability:
1. Synthetic Superdisintegrants
2. Natural Superdisintegrants.
1.4.3.1 Synthetic Superdisintegrants

A group of superdisintegrants including croscarmellose sodium (Ac-Di-Sol), sodium
starch glycolate (Primojel and Explotab) and crospovidone (Polyplasdone XL), use in fast
dispersible tablet because tablet shows excellent disintegration, wetting and other parameters.
ADVANTAGES OF SYNTHETIC SUPERDISINTEGRANTS

1. They are effective in lower concentrations,
2. Less effect on compressibility and flow ability,
3. More effective intra granularly.
Sodium Starch Glycolate: Brand Name: (Primogel, Explotab) [Shah R Et Al, 2013]
It is widely used in oral pharmaceuticals as a disintegrant in capsule and tablet formulations.
It is recommended to use in tablets prepared by either direct-compression or wet-
granulation processes. The recommended concentration in a formulation is 2-8%, with
the optimum concentration about 4% although in many cases 2% is sufficient.
The Disintegrant efficiency of sodium starch glycolate (SSG) is unimpaired upon

increasing the tablet compression pressure and in the presence of hydrophobic
excipients, such as lubricants unlike many other disintegrants. These are modified low
substituted carboxy methyl starches, available as explotab and primogel (shown in figure
1.6). Explotab is consisting of granules that rapid absorbed water leading to an enormous
increase in volume of granules result in rapid and uniform disintegration. The natural pre-
dried starches swell in water to the extent of 10-20 percent and the modified starches
increase in volume by 200-300 percent in water.

Crospovidone (Brand Name: Polyplasdone Xl)[Sethi V Et Al, 2012]

The cross-linked form of PVP is known as Crospovidone. Crospovidones are
synthetic, insoluble, cross-linked homopolymers of N-vinyl-2-pyrrolidone as shown in
Fig-1.7. When examined under scanning electron microscope, crospovidone particles appear
as granular and are highly porous. Due to its high crosslink density, crospovidone shows
rapid swelling in water, and pronounced hydration without forming gellarger particles
provide a faster disintegration than smaller particle.
Crospovidones are highly compressible materials as a result of their unique

particle morphology. Crospovidone is used as superdisintegrant at low concentration levels
(2-5%) in direct compression, wet and dry granulation processes. It is available in two
particle sizes in the form of Polyplasdone XL and Polyplasdone XL-10.
ADVANTAGES
1. Crospovidone uses a combination of swelling, wicking and deformation mechanismfor
rapid disintegration of tablets.
2. Swells rapidly in water without forming gel,
3. Highly compressible,
4. Rate and extent of liquid uptake and swelling of crospovidone (Polyplasdone XL 10)
are not reduced in 0.1 N hydrochloric acid when compared with aqueous medium.
Croscarmellose Sodium: (Brand Name: Ac-Di-Sol)[Deshmukh H Et Al, 2012]

Croscarmellose sodium is modified cellulose and is described as a cross-linked polymer
of carboxymethylcellulose. The degree of substitution of croscarmellose sodium is higher
than that of sodium starch glycolate, and the mechanism of cross linking is
different. The substitution is performed using Williamsons ether synthesis to give the
sodium salt of carboxymethylcellulose. Unlike the chemistry of SSG, the carboxymethyl
groups themselves are used to cross-link the cellulose chains, the process being
accomplished by dehydration. Thus the crosslinks are carboxyl ester links rather than
phosphate ester links as in Primojel.42 Cross linking makes it insoluble, hydrophilic, highly
absorbent material, resulting in excellent swelling properties and its unique fibrous nature
gives it excellent water wicking capability.

1.4.3.2 Natural Superdisintegrants[Mangal M et al, 2012]

These superdisinegrating agents are natural in origin and are preferred over
synthetic substances because they are comparatively cheaper, abundantly available, non-
irritating and non-toxic in nature. The natural materials like gums and mucilages have been
extensively used in the field of drug delivery for their easy availability, cost effectiveness,
Eco friendliness, emollient and non-irritant nature, and non-toxicity, capable of
multitude of chemical modifications, potentially degradable and compatible due to natural
origin. There are several gums and mucilages are available which have super-disintegrating
activity
1.4.4 Mechanism of Action Of Disintegrant[Pahwa R Et Al, 2010]

The tablet breaks to primary particles by one or more of the mechanisms listed below:
1. By capillary action b. By swelling
2. Because of heat of wetting d. Due to release of gases
3. By enzymatic action
4. Due to disintegrating particle/particle repulsive forces g. Due to deformation
Fig 1.5: Mechanism of Action Of Superdisintegrants

Water Wicking
The ability of disintegrant to draw water into the porous network of tablet is essential
for effective disintegration. On keeping the tablet into suitable aqueous medium, the
medium enters into tablet and replaces the air adsorbed on the particles which
weakens the intermolecular bonds and breaks the tablet into fine particles. Water uptake by
tablet depends upon hydrophilicity of the drug/excipients and on tableting conditions. Unlike
swelling, which is mainly a measure of volume expansion with accompanying force
generation, water wicking is not necessarily accompanied by a volume increase. The ability
of a system to draw water can be summarized by Washburns equation:

Swelling
Although water penetration is a necessary first step for disintegration, swelling is probably
the most widely accepted mechanism of action for tablet disintegrants. For swelling to be
effective as a mechanism of disintegration, there must be a superstructure against which
disintegrants swells.
Figure 1.4.4 represents the disintegration of tablet by wicking and swelling. Swelling of
the disintegrant against the matrix leads to development of a swelling force. A large
internal porosity in the dosage form in which much of the swelling can be accommodated
reduces the effectiveness of the disintegrant. On the other hand, sufficient swelling force is
exerted in the tablet with low porosity. It is worthwhile to note that if packing fraction is
very high, fluid is unable to penetrate in the tablet and disintegration is again slowed down.
Fig 1.6: Disintegration of Tablet By Wicking And Swelling
Heat of Wetting
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.
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.
Particle Repulsive Forces

This is another mechanism of disintegration that attempts to explain the swelling of
tablet made with non-swellabledisintegrants. Guyot-Hermann proposed a particle-particle
repulsion theory to explain the observation that particles which do not swell extensively
such as starch, could still disintegrates tablets.
According to this theory, water penetrates into tablet through hydrophilic pores and
a continuous starch network is created that can convey water from one particle to the
next, imparting a significant hydrostatic pressure. The water then penetrates between starch
grains because of its affinity for starch surfaces, thereby breaking hydrogen bonds and
other forces holding the tablet together. The electric repulsive forces between particles are
the mechanism of disintegration and water is required for it.
Deformation Recovery
Deformation recovery theory implies that the shape of disintegrant particles is distorted
during compression and the particles return to their pre-compression shape upon wetting,
thereby causing the tablet to break apart. Such a phenomenon may be an important
aspect of the mechanism of action of disintegrants such as crospovidone and starch that
exhibitlittle or no swelling.
Fig 1.7: Disintegration by Deformation and Repulsion

1.5 Formulation Techniques for Designing Fast Disintegrating Tablets
Fig 1.8: Different Types of Techniques Design for MDT
1.5.1CONVENTIONAL METHODS
1. Spray Drying
A highly porous and fine powder is prepared by spray drying an aqueous
composition containing support matrix and other components. This is then mixed with active
ingredient and compressed into tablet. Allen and wang used this technique to prepare
mouth dissolving tablets, which disintegrated within 20 sec. [Mizumoto T. et al , 1996]
2. Freeze Drying
The tablets prepared by freeze drying or lyophilization are very porous in nature
and disintegrate or dissolve rapidly when come3 in contact with saliva. In this process,
water is sublimated from the product after freezing. First of all, the material is frozen to
bring it below its eutectic point. Then primary drying is carried out to reduce the moisture to
around 4% w/w of dry product. Finally, secondary drying is done to reduce the bound
moisture to the required volume. Due to lyophilization, bulking agent and sometimes drug
acquire glossy amorphous structure and thus dissolution is enhanced. A tablet that
rapidly disintegrates in aqueous solution includes a partially collapsed matrix network that
that has been vacuum dried above the collapsed temperature of the matrix. The matrix is
partially dried below the equilibrium freezing point of the matrix. Vacuum during the tablet
above its collapse temperature, instead of freeze drying below its collapse temperature
provides a process for producing tablets with enhanced structural integrity, while rapidly
disintegrating in normal amounts of saliva. However the use of freeze drying is

limited due to high cost of equipment and processing. Other major disadvantage of the
final dosage forms includes lack of physical resistance in standard blister
packs. [Bhowmik D. et al ,2009]
3. Effervescence
Addition of an effervescent system in the formulation is one of the approaches by
which Mouth Dissolving tablets can be prepared. The major advantages of this method are it
is well established, easy to implement and masks the bitter taste of the drug. The
effervescent system is generally composed of a dry acid and dry base which when
react facilitate a mild effervescent action when the tablet contacts saliva. The
effervescent reaction accelerates the disintegration of tablet through the release of carbon
dioxide, water and salt.[Pather SI et al, 2001] Due to the evolution of carbon dioxide,
the bitter taste of the drug is also masked and a pleasant mouth feel is felt. These
systems mainly use dry acids like citric acid and tartaric acid, and dry bases like sodium
bicarbonate.
The major drawbacks of this method include chemical stability, for which controlled
humidity conditions required and storage conditions like temperature and hygroscopicity.
4. Tablet Moulding
Tablets prepared by this method are solid dispersions. Physical form of drug in the
tablets depends on whether and to what extent it dissolves in the wetted mass. The drug can
exist as discrete particles or micro particles in the matrix. It can dissolve totally to
form a solid solution or dissolve partially in a molten carrier and remaining, if any, stays
undissolved and dispersed in the matrix. Disintegration time, drug dissolution rate and
mouth feel will depend on the type of dispersion.
Moulded tablets pose porous structure, which facilitates rapid disintegration and
easy dissolution. Moulded tablets offer improve taste due to water soluble sugars
present in dispersion matrix. But moulded tablets lack good mechanical strength and
can undergo breakage or erosion during handling and opening of blister packs. However,
adding sucrose, acacia or polyvinyl pyrrolidone can increase mechanical strength.
[KaurTejvir et al 2011]

5. Sublimation
This process involves addition of some inert volatile substances like urea,
urethane, naphthalene, camphor, etc. to other expedients and the compression of blend
into tablet. Removal of volatile material by sublimation creates pores in tablet structure,
due to which tablet dissolves when comes in contact with saliva. Additionally
several solvents like cyclohexane, benzene etc can also be used as pore forming agents.
Mouth dissolving tablets with highly porous structure and good mechanical strength
have been developed by this method. [YarwoodRj et al , 1998] In studies conducted

by Heinemann and Rothe., 1975, Knitsch et al., 1979 inert solid ingredients that displayed
high volatility (e.g., ammonium bicarbonate, ammonium carbonate, benzoic acid,
camphor, naphthalene, phthalic anhydride, urea, and urethane) were compressed along
with other excipients into a tablet. The volatile material was then removed by sublimation,
leaving behind a porous matrix.[Heinmanne et al , 1975]
FIG 1.9: Step Involved In Sublimation

6. Direct Compression
Direct compression is one of the popular techniques for preparation of these dosage
forms. The advantages of this method include easy implementation, use of conventional
equipments along with commonly available excipients, limited number of processing
steps and cost effectiveness.Disintegration and solubilization of directly compressed tablets
depend on single or combined action of disintegrants, water-soluble excipients and
effervescent agents. The basic principle involved in development of these dosage
forms using this technique is addition of superdisintegrants in optimum concentrations
so as to achieve rapid disintegration along with pleasant mouth feel. It is considered as the
best method to prepare orally disintegrating dosage forms since the prepared tablets offer

higher disintegration due to absence of binder and low moisture contents. This approach is
also considered as disintegrant addition technology.[Pahwa R etal,2010]
1.5.2 Patented Technologies

1. Zydis Technology
It is patented by R.P. Scherer, Inc., and it is the first generations of fast disintegrating
dosage forms. There are approximately 12 marketed ZYDIS products, including
lorazepam, piroxicam, loperamide, loratidine, enalapril and selegiline.[Sastry SV et al,

2000]
Description of Dosage Form and Mode of Drug Release

Zydis is a tablet-shaped dosage form that spontaneously disintegrates in the mouth in
seconds. This is due to the characteristically high porosity produced by the freeze-drying
process used in its manufacture. The highly porous structure allows the rapid ingress of
saliva, which quickly dissolves the soluble excipients, releasing the drug particles as a
suspension or solution is placed on the tongue. The suspension is then swallowed and the
drug absorbed in the normal way.
Zydis Oral Fast-Dissolving Dosage Form[Alaxander A et al, 2010]

These formulations are freeze-dried products of a combination of water-soluble
matrix material with drug, which is prefilled in blister pockets and freeze dried to remove
the water by sublimation. The resultant structures are very porous in nature and rapidly
disintegrate or dissolve upon contact with saliva. The process had undergone several
modifications to accommodate drugs with different physicochemical characteristics, drug
loading and particle size, and matrix modifications to result in an acceptable dosage form.
Drug loading for water insoluble drugs approaches 400 mg. The ideal drug characteristics
are relative water insolubility with fine particle size and good aqueous stability in the
suspension. As the dose is increased, it becomes more difficult to achieve the optimum
formulation. The upper limit for drug loading is much lower (approximately 60 mg) for
water soluble drugs. The primary problems associated with water soluble drugs are the
formation of eutectic mixtures, resulting in freezing-point.depression and the formation of a
glassy solid on freezing which might collapse on drying because of loss of the
supporting structure during the sublimation process.

The addition of crystal-forming agents such as mannitol, which induce crystallinity and
hence impart rigidity into the amorphous material, can be employed to prevent the
collapse of the structure. The soluble drugs can be complexed with ion exchange
resins to prevent the collapse of the structure, which is also useful in masking the bitter
taste of medicaments.
Zydis Manufacturing Process[Alaxander A et al, 2010]

The commercial Zydis manufacturing process, is outlined in Figure 1.3, consists of the
steps described below.
a) Preparation of Drug Suspension/Solution

A vacuum mixer is used to first prepare the aqueous solution of excipients and then to
add and disperse the active ingredient by high shear homogenization. Once prepared,
the solution or dispersion is transferred to a holding vessel.
b) Forming-Filling
The drug suspension is circulated from the holding vessel through a manifold
supplying a series of positive displacement pumps. These pumps deliver the required
volume of material along the delivery lines into the blister pockets, which are preformed
in a continuous ribbon of plastic laminate.
c) Freezing
After the blister pockets are filled, the blister ribbon is cut into short lengths, called
trays which are transferred on a conveyor through the freeze tunnel. The cold nitrogen
atmosphere freezes the product within minutes. This flash freezing fixes the
homogeneity of the components and creates the appropriate ice product.
Crystal structure determines the porosity of the final product. The frozen product is
collected and transferred to a series of refrigerated storage cabinets to maintain it in
the frozen state prior to loading into the freeze dryer.

Fig 1.10: Schematic Representation of Zydus Manufacturing Process
d) Freeze Drying
The trays containing the frozen product are loaded onto the shelves of the freeze dryer
and the ice removed by sublimation at low pressure. The dryers are characterized by a short
inter shelf spacing, which maximizes the product loading and accelerates the drying
process. Typical drying times are on the order of 5 hours or long-term storage. Zydis
products are packed in blister packs to protect the formulation.
e) Blister Lidding
The dried product is then sealed into the blister pockets by application of the lidding foil
and the blister pack is then punched out to the required format.
Collapse protectants such as glycine prevent the shrinkage of zydis units during freeze-
drying process from moisture in the environment and long term storage.
2. ORASOLV (Cima Labs, Inc.)

ORASOLV was Cima's first generation fast-dissolving/disintegrating dosage
form. ORASOLV utilizes effervescence material and taste-masked active ingredients, and
requires only conventional manufacturing equipment.
By definition, the effervescence is a chemical reaction between an organic acid (citric

acid, fumaric acid or maleic acid) and a base (sodium bicarbonate, potassium
bicarbonate or magnesium bicarbonate), thereby resulting in the generation of carbon
dioxide. The time for the disintegration of OraSolv tablets within the oral cavity varies from 6
s to 40 s, depending largely on tablet size and the compression force (within the lower

range) that was used to form the tablet. The low compression force leads to high tablet
porosity which, in turn, accelerates the rate of disintegration of the tablet and
dissolution of the water-soluble excipients. The active ingredients can be taste-masked
using a variety of techniques such as fluid bed coating, microencapsulation, or spray
congealing. Because the OraSolv tablets are produced at low compression forces, they are
soft and friable.
To reduce handling risks of the tablets, the tableting and packaging processes are
integrated and a specially designed package is used. The packaging system consists of a
robot that picks up and places the tablets in dome-shaped depressions in aluminum foil. A
layer of top foil is heat-sealed over the bottom foil. The integrated manufacturing line is
equipped with a printing assembly that enables each blister card to be printed
individually during the manufacturing process. The automated system then cuts the foil
into cards of, usually, six tablets.
Fig 1.11: Showing Marketed Formulation Of Orasolv
A robot eye detects depressions that do not contain tablets and rejects these cards.
The operator may also observe unfilled cards on a monitor. The specially designed
package and processing system, referred to as Pak-Solv, protects the OraSolv tablets from
breaking and attrition during the rigors of shipping. In particular, the dome-shaped
depressions limit the vertical movement of the tablet within the package since the diameter
of the lower portion of the dome is too narrow to accommodate the tablet, thus the tablet
remains in the upper part of the dome adjacent to the top foil. This is in contrast to a regular
blister package in which the sides of the depression are vertical and the bottom is flat,
allowing a greater range of vertical movement. Pak-Solv also offers light, moisture, and
child resistance. Moisture resistance is important when packaging an effervescent
formulation or moisture-sensitive drugs.36

3. Durasolv (Cima Labs, Inc.)[Alaxander A Et Al, 2010]

DuraSolv is Cimas second-generation fast-dissolving tablet technology. Like OraSolv,
the Dura Solv tablets consist of water-soluble excipients and are manufactured using
direct compression techniques. However, DuraSolv utilizes non-directly compressible fillers
in fine particle form these fillers have a high surface area, which increases their dissolution
rate. The incorporation of a high proportion of such fillers causes the tablet to melt or
dissolve, rather than disintegrate. Wicking agents assist the entry of water into the body of
the tablet, whereas swelling disintegrants are avoided or used in small proportions.
The increased dissolution rate of the soluble, fine-particle filler compensates for the
reduction in tablet porosity due to the use of higher compression forces (relative to
the OraSolv products). The manufacturing process utilizes conventional blenders and
high-speed tablet presses.
4. Wowtab (Yamanouchi Pharma Technologies, Inc.) [Alaxander A Et Al, 2010]

Wow tab 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 and 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 highly moldable characteristics.20 Simple
physical mixing of a mannitol and maltose combination did not result in a tablet with the
required qualities. The process of granulation, in which low moldable sugar is coated with
high moldable sugar followed by a specific humidity treatment, is required to achieve
fast disintegration performance characteristics. The resulting tablet had a hardness of at least

1.0 2.0 kg (tablet-size dependent) and presented a preferable disintegration time of 140
seconds (typical values of <15 s). Various drug classes can be incorporated into the above
combination to achieve a fast disintegrating tablet with proper performance characteristics.
A preferable ratio of 510% by weight of high moldable sugar was found to be sufficient
to achieve the desired level of tablet hardness with rapid disintegration.
Others Patented Technologies for Fast Dissolving Drug Delivery Systems

1. FlashDose (Fuisz Technologies, Ltd.)
2. Flashtab (Prographarm Group)
3. OraQuick (KV Pharmaceutical Co., Inc.)
4. Ziplets/Advatab, (Passano con Barnago, Italy)
5. Lyoc technology (PHARMALYOC)
6. Pharmaburst technology (SPI Pharma, New Castle)
7. Frosta technology (Akina)
5. Flashdose(Fuisz Technologies, Ltd. Chantilly, VA, USA)

The FLASHDOSE dosage form utilizes the Shearform technology in association
with Ceform TI technology as needed, to eliminate the bitter taste of the
medicament. The Shearform technology is employed in the preparation of a matrix known
as floss, which is made from a combination of excipients, either alone or in combination
with drugs. The floss is a fibrous material similar to cotton-candy fibers, commonly made
of saccharides such as sucrose, dextrose, lactose and fructose31. For the preparation of
sucrose fibers, temperatures ranging from 180266 0F are employed. However, the use of
other polysaccharides such as poly-maltodextrins and poly-dextrose can be transformed
into fibers at 3040% lower temperatures than those used for sucrose fiber production.
This modification permits the safe incorporation of thermo-labile drugs into the
formulation32.The manufacturing process can be divided into the four steps detailed below
Floss Blend
Initially, approximately 80% sucrose in combination with mannitol or dextrose
and approximately 1% surfactant is blended to form the floss mix. The surfactant acts
as a crystallization enhancer in maintaining the structure and integrity of the floss
fiber. The enhancer also helps in the conversion of amorphous sugar into crystalline sugar,
from an outer portion of amorphous Shearform sugar mass, and subsequently converting
the remaining portion of the mass to complete crystalline structure. This process helps to

retain the dispersed active ingredient in the matrix, thereby minimizing migration out of the
mixture
a) Floss Formation
The matrix is produced by subjecting the carrier material to flash heat and flash
flow processing in a heat processing machine. The floss formation machine is similar to a
cotton-candy fabricating type, consisting of a spinning head and heating elements. In the
flash heat process, the carrier material is heated sufficiently to create an internal flow
condition, followed by its exit through the spinning head that flings the floss by
centrifugal forces generated by rotation.
Fig 1.12- Representation of FLASHDOSE Technology
The spinning head rotates at approximately 20003600 rpm, providing sufficient

centrifugal forces. Heating blocks are positioned around the circumference as a series of
narrow slots located between the individual heating blocks. A series of grooves located
on the inner circumference of the crown and configured on the outside of the rim of the
heaters, narrow the width of the aperture while increasing the path length of the exiting
material, resulting in the production of fibers. The material is essentially heated upon
contact with heaters, flows through the apertures under centrifugal forces, and draws
into long, thin floss fibers. The produced fibers are usually amorphous in nature.
b) Floss Chopping and Conditioning.

The fibers are conditioned to a smaller particle size by chopping and rotation action in a
high shear mixer-granulator. The conditioning is performed by partial crystallization
through an ethanol treatment (1%) sprayed on to the floss that is subsequently evaporated,
resulting in floss with improved flow and cohesive properties31.

c) Tablet Blend and Compression.

The chopped and conditioned floss fibers are blended with active ingredient along with
other standard tableting excipients, such as lubricants, flavors and sweeteners. The resulting
mixture is compressed into tablets. The active can also be added to the floss blend before
subjecting it to the flash heat process.
6. Flashtab (Prographarm Group)

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 tableting
technology. In this technology, two types of disintegrants are used:
1. A disintegrating agent that has a high swelling force and
2. A swelling agent that has a low swelling force.
7. Oraquick Technology[Nandy BC Et Al, 2011]

The OraQuick fast-dissolving/disintegrating tablet formulation utilizes a patented
taste masking technology. KV Pharmaceutical claims its microsphere technology
known as MicroMask, has superior mouth feel over taste masking alternatives. 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.
KV Pharmaceutical also claims that the matrix that surrounds and protects the drug
powder in microencapsulated particles is more pliable, meaning tablets can be compressed
to achieve significant mechanical strength without disrupting taste masking.
8. AdvaTab technology[Patel PB et al, 2006]

This technology is patented by passano con Barnago, Italy. It utilizes water-
insoluble ingredient combined with one or more effective disintegrants to produce ODT
with improved mechanical strength and optimal disintegration time at low
compression force. This technology handles high drug loading and coated drug particles
and does not require special packaging, so they can be packed in push through blisters or
bottles.

9. LYOC Technology
It is patented by PHARMALYOC. Oil in water emulsion is prepared and placed directly in
to blister cavities followed by freeze drying. Non- homogeneity 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.
10. Frosta Technology[Fu Y Et Al, 2004]

Akina patents this technology. It utilizes the concept of formulating plastic granules
and compressing them at low pressure to produce strong tablets with high porosity.
Plastic granules composed of porous and plastic material, water penetration enhancer, and
binder. The process involves mixing the porous plastic material with water penetration
enhancer followed by granulating with binder. The tablets obtained have excellent
hardness and rapid disintegration time ranging from 15 to 30 sec depending on size of
tablet.
11. Quick sol technology[Sayeed A Et Al, 2011]

This technology is patented by Janssen Pharmaceutical. 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.

Table 1.1: List of Marketed Fast Dissolving Tablets [Kumar V . Dinesh Et Al , 2011]
TRADE NAME ACTIVE DRUG MANUFACTURER

Felden Fast Melt Piroxicam Pfiserinc.,NY,USA
Claritin Redi Tab Loratidine Schering Plogh Corp.,Usa
Maxalt MLT Rizatriptan Merck And Co.,NJ , USA
Zyprexia Olanzapine Eli Lilly , Indianapolis,Usa
Pepcid RPD Famotidine Merck And Co.,NJ USA
Zofran FDT Ondansetron Glaxo Welcome , Middlesex ,UK
Zoming-ZMT Zolmitriptan Astrazeneca, Wilmington, USA
TempraQuiclets Acetaminofen Bristol Myers Squibb, NY,USA
Febrectol Paracetamol Prographarm,Chateauneuf,France
Torrox MT Rofecoxib Torrent Pharmaceuticals, India
OlanexInstab Olanzapine Ranbaxy Lab Ltd. New Delhi , India
Romilast Montelukast Ranbaxy Labltd. New Delhi,India
Diphenhydramine
BenadryFastmelt Warner Lambert , NY, USA
And Pseudoephedrine
Nurofen Flash Tab Ibuprofen Ethypharm
TempraQuicklets Paracetamol CimaLabs,Inc.
ZolmigRepimelt Zolmitriptan CimaLabs,Inc.
Cibalgina Due Fast Ibuprofen Eurand International
Allegra ODT Fexofenadine Sanofi Aventis
Aricept ODT Donepezil Eisai Co.
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World Journal of Pharmaceutical Research

Singh et al. World Journal of Pharmaceutical Research

Volume 3, Issue 7, 755-791. Review Article ISSN 2277 7105

A REVIEW ON MOUTH DISSOLVING TABLET USING DIFFERENT

Kamla Nehru Institute of Management And Technology, Faridipur, Sultanpur.

www.wjpr.net Vol 3, Issue 7, 2014. 755

formulation of drugs for oral delivery for improving their action.

Keyword: Mouth Dissolving Tablet, Synthetic Superdisintegrants, Natural

1.1 Drug Delivery Systems [Jain kewal k. ,2007]

1.1.1 Drug Delivery Routes [Jain kewal k. ,2007]

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A classification of various anatomical routes for systemic drug delivery

Oral Drug Delivery [Jain kewal k. ,2007]

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appearance. [Aulton M. E. 2, 2009]

Tablets are popular for several reasons:

1.2.1 Classification Of Tablets: [Aulton M. E. 2 , 2009]

www.wjpr.net Vol 3, Issue 7, 2014. 758

disintegrating tablet in a sequence of processes, including tablet disintegration, drug

www.wjpr.net Vol 3, Issue 7, 2014. 759

Sublingual and Buccal Tablets

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1.3 Mouth Dissolving Tablets

active people.[Arjun G. et al, 2010]

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1.3.1 Mechanism Of Absorption Of Drug Through Mouth:[SiddiquiNehalet al, 2011]

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1.3.3 Requirements of Fast Disintegrating Systems [Sahoo S Et Al, 2010],[Siddiqui MN

1.3.4 Advantage of Fast Dissolving Tablets [Reddy LH Et Al, 2002]

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FIG 1.2 : Advantages of MDT

1.3.5 Limitations of Fast Disintegrating Tablets[Bhowmik D Et Al, 2009],[Shaikh S Et

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1.3.6 Overview of Oral Cavity[Toratoragorahowski, 2001]

FIG-1.3 Structure of Oral Cavity

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1.3.7 Desired Characteristics & Development Challenges Of FDTs: [Prakashv Et Al,

Tablet Strength and Porosity

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Taste of Active Ingredients

Taste-masking technologies are increasingly focused on aggressively bitter-tasting drugs

1.4Super disintegrants[Pahwa R Et Al, 2010]

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FIG 1.4: Mechanism of Tablet Disintegration

1.4.1 Selection of Super disintegrants[Pahwar Et Al, 2010]

1.4.2 Method of Incorporation of Super disintegrants[Mangal M Et Al, 2012]

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1.4.3 Types of Superdisintegrants[Shah R Et Al, 2013]

1.4.3.1 Synthetic Superdisintegrants

ADVANTAGES OF SYNTHETIC SUPERDISINTEGRANTS

The Disintegrant efficiency of sodium starch glycolate (SSG) is unimpaired upon

www.wjpr.net Vol 3, Issue 7, 2014. 769

Crospovidone (Brand Name: Polyplasdone Xl)[Sethi V Et Al, 2012]

Crospovidones are highly compressible materials as a result of their unique

Croscarmellose Sodium: (Brand Name: Ac-Di-Sol)[Deshmukh H Et Al, 2012]

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1.4.3.2 Natural Superdisintegrants[Mangal M et al, 2012]

1.4.4 Mechanism of Action Of Disintegrant[Pahwa R Et Al, 2010]

Fig 1.5: Mechanism of Action Of Superdisintegrants

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Fig 1.6: Disintegration of Tablet By Wicking And Swelling

Due To Release of Gases

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temperature, strict control of environment is required during preparation of the tablets.