CHAPTER-1 INTRODUCTION

Introduction:

The oral route of drug administration is the most popular and successfully route used for

conventional delivery of drugs. The tablet is the most widely used dosage form because of its

convenience in terms of self-administration, low cost and ease in manufacturing. However,

geriatric and pediatric patient experience difficulty in swallowing conventional tablets, which

leads to poor patient compliance. 1 For these formulations, the small volume of saliva is

usually sufficient to result in tablets disintegrating in oral cavity. Often times people

experience inconvenience in swallowing conventional dosage forms such as tablets when

water is not available, in motion sickness and sudden episodes of coughing during the

common cold, allergic conditions and bronchitis. The medication can be absorbed partially or

entirely into the systemic circulation from blood vessels in the sublingual mucosa, or it can

be swallowed as a solution to be absorbed from gastrointestinal tract. 2 Many patients express

difficulty in swallowing tablets and hard gelatin capsules, resulting in noncompliance and

ineffective therapy.3

Fast dissolving Tablets

Fast disintegrating dosage forms are defined as drug delivery systems that dissolve or

disintegrate within seconds to a few minutes. The fast disintegrating dosage forms systems

include tablets, films, wafers, caplets, granules, and powders. The super-disintegrants speed

up moisture penetration and dispersion of matrix there by increasing the disintegration rate of

drug delivery system. On contact with water they swell, hydrate, increase volume or form

and produce a disruptive change in tablets which results in its fast disintegration. In these

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cases, the bioavailability and onset of action of drugs from fast disintegrating dosage forms is

greater compared to the standard oral dosage forms.4

United States Food and Drug Administration (FDA) defined fast dissolving tablet (FDT) as a

solid dosage form containing medicinal substance or active ingredient which disintegrate

rapidly within a matter of seconds when placed upon the tongue. Fast dissolving tablet are

also known as mouth-dissolving tablets, melt-in mouth tablets, quick dissolving tablet. Fast

dissolving tablets dissolve or disintegrate in the oral cavity without the need of water.5

FDTs are prepared by various techniques, mainly direct compression, lyophillization and

moulding. The simplicity and cost effectiveness of the direct compression process have

positioned this technique as an attractive alternate to traditional granulation technologies.6

IDEAL PROPERTIES OF FAST DISSOLVING TABLETS

i. The tablets should disintegrate or dissolve in the mouth (in saliva) within few

seconds.

ii. Should not require water or any liquids to swallow or to show its action.

iii. Should allow high drug loading.

iv. Should be compatible with taste masking and other excipients.

v. Should have pleasing mouth feel.

vi. Should not leave any residue in the mouth after administration.

vii. Should have low sensitivity to environmental conditions (temperature, humidity, etc.)

viii. Should be adoptable to existing processing and packaging machinery.

ix. Excipients should have high wettability.

x. Should have rapid drug absorption from the pre-gastric area i.e. mouth, pharynx and

oesophagus, producing rapid onset of action.

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xi. Should allow packaging equipments at low cost.

xii. Should have sufficient strength to withstand rigors of the manufacturing process and

post manufacturing handling.

xiii. Be harder and less friable.7

SALIENT FEATURES OF FDT

i. does not require water for oral administration

ii. have sufficient strength to withstand the rigors of the manufacturing process and post

manufacturing handling

iii. allow high drug loading

iv. insensitive to environmental conditions such as humidity and temperature

v. adaptable and amenable to existing processing and packaging machineries

vi. cost effective.

vii. have a pleasant mouth feel.5

Merits of Fast dissolving Tablets

i. Improved compliance/added convenience

ii. No water needed

iii. No chewing needed

iv. Better taste

v. Improved stability

vi. Suitable for controlled as well as fast release actives

vii. Allows high drug loading

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

ix. Adaptable and amenable to existing processing and packaging machinery

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x. Cost- effective.5

Demerits of Fast Dissolving Tablets

i. Drugs with relatively large doses are difficult to formulate into FDTs.

ii. Patients who concurrently take anti-cholinergic medications may not be the best

candidates for FDTs.

iii. Tablets usually have insufficient mechanical strength. Hence, it requires careful

packaging

iv. and handling

v. Tablets may leave unpleasant taste and/or grittiness in mouth if not formulated

properly.

vi. They are more susceptible to degradation by humidity and temperature.

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

viii. Some time it possesses mouth feeling.

ix. MDT requires special packaging for properly stabilization & safety of stable product.

x. Drugs difficult to formulate into FDT with relatively larger doses.

xi. Drugs with short half-life and frequent dosing and those whom require controlled or

xii. sustained release are unsuitable candidates of FDT.8

CHALLENGES IN FORMULATION OF FAST DISSOLVING TABLETS (FDTS)

Mechanical strength and disintegration time

It is obvious that increasing the mechanical strength will delay the disintegration time. So a

good compromise between these two parameters is always essential. FDTs are formulated to

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obtain disintegration time usually less than a minute. While doing so, maintaining a good

mechanical strength is a prime challenge.

Taste masking

As most drugs are unpalatable, rapid disintegrating drug delivery systems usually contain the

medicament in a taste masked form. Delivery systems disintegrate or dissolve in patient’s

oral cavity, thus releasing the active ingredients which come in contact with the taste buds;

hence, taste-masking of the drugs becomes critical to patient compliance.

Aqueous solubility

Water-soluble drugs pose various formulate ion challenges because they form eutectic

mixtures, which result in freezing-point depression and the format ion of a glassy solid that

may collapse upon drying because of loss of supporting structure during the sublimate ion

process. Such collapse sometimes can be prevented by using various matrix-forming

excipients such as mannitol than can induce crystallinity and hence, impart rigidity to the

amorphous composite .

Hygroscopicity

Hygroscopicity is, of course, an important characteristic of a powder. It can be shown,

roughly, for a fairly soluble compound that 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

created to protect FDTs from various environmental conditions.

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Amount of drug

The application of technologies used for FDTs is limited by the amount of drug that can be

incorporated into each unit dose. For lyophilized dosage forms, the drug dose must be lower

than 400 mg for insoluble drugs and less than 60 mg for soluble drugs. This parameter is

particularly challenging when formulating a fast-dissolving oral films or wafers.

Size of table

It has been reported that the easiest size of tablet to swallow is 7-8 mm while the easiest size

to handle was larger than 8 mm. Therefore, the tablet size that is both easy to take and easy to

handle is difficult to achieve.

Mouth feel

FDTs should not disintegrate into larger particles in the oral cavity. The particles generated

after disintegration of the FDTs should be as small as possible. Moreover addition of flavours

and cooling agents like menthol improve the mouth feel.

Sensitivity to environmental conditions

FDTs should exhibit low sensitivity to environment conditions such as humidity and

temperature as most of the materials used in FDTs are meant tom dissolve in minimum

quantity of water.8

Montelukast sodium is an anti-asthmatic, it mainly prevents leukotriene mediated effect

associated with asthma and allergic arthritis. Mouth dissolving tablets of montelukast sodium

was prepared by direct compression method using superdisintegrants such as croscarmellose

sodium and crospovidone. The compatibility of the drug in the formulations was confirmed

by IR studies. The formulations were subjected to precompression and postcompression

parameters and the results were found to be within acceptable limits. The formulated tablets

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disintegrated in less than 26.33 sec fulfilling the official requirements for dispersible tablets.

The rapid drug dissolution was observed in the formulations containing croscarmellose

sodium and followed first order release kinetics. Finally, it can be concluded that mouth

dissolving tablets of montelukast sodium can be prepared by direct compression method

using croscarmellose sodium as superdisintegrant9

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