ORAL DISINTEGRATING TABLETS

Agus Siswanto

Oral Disintegrating Tablets

A solid dosage form containing medicinal
substance or active ingredient which
disintegrates rapidly usually within a matter of
seconds when placed upon the tongue (FDA)
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 (European
Pharmacopoeia )

Drug selection criteria

Ability to permeate the oral mucosa
At least partially non-ionized at the oral cavity pH
Have the ability to diffuse and partition into the
epithelium of the upper GIT
Small to moderate molecular weight
Low dose drugs preferably less than 50 mg
Short half life and frequent dosing drugs are unsuitable
for ODT
Drug should have good stability in saliva and water
Very bitter or unacceptable taste and odor drugs are
unsuitable for ODT

Choice of drug candidate

No bitter taste
Good stability in water and saliva
Dose should be low as possible

Unsuitable drug candidate for orally disintegrating

tablet should include:
Short half-life and frequent dosing
Drug having very bitter taste
Required controlled or sustained release

Advantages of ODT
Improved patient compliance
Rapid onset of action and may offer an improved
bioavailability
Useful for pediatric, geriatric and psychiatric patients
Suitable during traveling where water is may not be
available
No specific packaging required, can be packaged in
push through blisters
Smooth mouth feel and pleasant taste
Conventional manufacturing equipment
Cost effective
Good chemical stability as conventional oral solid
dosage form

Characteristics of an Ideal ODT

Utilizes cost effective production method
Require no water for oral administration
Dissolve / disperse/ disintegrate in mouth in a
matter of seconds
Have a pleasing mouth feel and taste masking.
Less friable and have sufficient hardness
Leave minimal or no residue in mouth after
administration
Manufacturing using conventional manufacturing
method

Basic approaches to develop Oral Disintegrating Tablets

porous structure

highly water-soluble
excipients

appropriate disintegrating
agents

Techniques in preparation of ODT

1. Freeze drying or
7. Moulding
Lyophilization
8. Nanonization
2. Spray Drying
9. Fast Dissolving Films
3. Direct Compression 10. Phase transition
4. Sublimation
process
5. Cotton Candy Process 11. Melt granulation
6. Mass Extrusion

Freeze drying or Lyophilization

Lyophilization means drying at low temperature under
condition that involves the removal of water by
sublimation
Drug in a water soluble matrix which is then freeze
dried to give highly porous structure
The tablets prepared by lyophilization disintegrate
rapidly in less than 5 seconds due to quick penetration
of saliva in pores when placed in the oral cavity
Lyophilization is useful for heat sensitive drugs i.e.
thermo-labile substances
Ex. Loratidine (Claritin Reditab and Dimetapp Quick
Dissolve)

Freeze drying or Lyophilization

Spray drying
Spray drying can produce highly porous and fine
powders that dissolve rapidly
This technique is based on a particulate support
matrix, which is prepared by spray drying an
aqueous composition containing support matrix
and other components to form a highly porous
and fine powder
This then mixed with active Ingredients and
compressed into tablets
Ex. Hyoscyamine Sulfate ODT

Spray drying

Direct compression
This is most popular technique because of its easy
implementation and cost-effectiveness
Direct compression represents the simplest and most cost
effective tablet manufacturing technique

This technique can now be applied to preparation of

ODT because of the availability of improved excipients
especially superdisintegrants and sugar based
excipients
The basic principle involves addition of disintegrants
and/or water soluble excipients and/or effervescent
agents
Superdisintegrants in optimum concentration (about 25%) are mostly used so as to achieve rapid
disintegration along with the good mouth feel

(a) Superdisintegrants
In many orally disintegrating tablet
technologies based on direct compression, the
addition of superdisintegrants principally
affects the rate of disintegration and hence
the dissolution
The presence of other formulation ingredients
such as water-soluble excipients and
effervescent agents further hastens the
process of disintegration

Mechanism of Superdisintegrants
Swelling
Porosity and capillary action (Wicking)
Due to disintegrating particle/particle
repulsive forces
Due to deformation

1. Swelling
Perhaps the most widely accepted general mechanism
of action for tablet disintegration is swelling
Tablets with high porosity show poor disintegration
due to lack of adequate swelling force
On the other hand, sufficient swelling force is exerted
in the tablet with low porosity
It is worthwhile to note that if the packing fraction is
very high, fluid is unable to penetrate in the tablet and
disintegration is again slows down

2. Porosity and capillary action

(Wicking)
Disintegration by capillary action is always the first
step.
When we put the tablet into suitable aqueous medium,
the medium penetrates into the tablet and replaces
the air adsorbed on the particles, which weakens the
intermolecular bond and breaks the tablet into fine
particles.
Water uptake by tablet depends upon hydrophilicity of
the drug /excipient and on tableting conditions.
For these types of disintegrants maintenance of porous
structure and low interfacial tension towards aqueous
fluid is necessary which helps in disintegration by
creating a hydrophilic network around the drug
particles

3. Due to disintegrating
particle/particle repulsive forces
Another mechanism of disintegratn 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.
Researchers found that repulsion is secondary to
wicking.

4. Due to deformation
During tablet compression, disintegranted particles get
deformed and these deformed particles get into their
normal structure when they come in contact with
aqueous media or water.
Occasionally, the swelling capacity of starch was
improved when granules were extensively deformed
during compression.
This increase in size of the deformed particles produces
a break up of the tablet.
This may be a mechanism of starch and has only
recently begun to be studied.

(b) Sugar Based Excipients

This is another approach to manufacture ODT
by direct compression
The use of sugar based excipients especially
bulking agents 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 sugar-based

excipients into two types on the basis of
molding and dissolution rate
Type 1 saccharides
exhibit low mouldability but high dissolution rate
lactose and mannitol

Type 2 saccharides
exhibit high mouldability and low dissolution rate
maltose and maltilol

MANUFACTURING STEPS FOR DIRECT COMPRESSION

Sublimation
This technique is based on the use of volatile
ingredients (e.g. camphor, ammonium
bicarbonate, naphthalene, urea, urethane
etc.) to other tablet excipients and the
mixture is then compressed into tablets
Entrapped volatile material is then removed
via sublimation, which leads to formation of a
porous structure
Ex. Phloroglucinol Hydrate (Spasfon Lyoc)

Steps Involved in sublimation

Cotton candy process

Involves the formation of matrix of
polysaccharides by simultaneous action of
flash melting and spinning
This candy floss matrix is then milled and
blended with active ingredients and
excipients after re-crystallization and
subsequently compressed to FDT
Characteristics: It can accommodate high doses
of drug and offers improved mechanical strength
Ex- Tramadol HCl (Relivia Flash dose)

Mass-Extrusion
Involves softening the active blend using the
solvent mixture of water soluble polyethylene
glycol, methanol and expulsion of softened
mass through the extruder or syringe to get a
cylindrical shape of the product into even
segments using heated blade to form tablets
Characteristics: The dried product can be used
to coat granules of bitter tasting drugs and
thereby masking their bitter taste
Ex. Zolmitriptan (Zolmig ZMT)

Moulding
water-soluble ingredients with a hydroalcoholic solvent is used and is molded
into tablets under pressure lower than that
used in conventional tablet compression
Characteristics: Molded tablets are very
less compact than compressed tablet
porous structure that enhances
disintegration/ dissolution and finally
absorption increased

Nanonization
Involves size reduction of drug to nanosize 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 FDTs
Characteristics: It is used for poorly water soluble drugs
It leads to higher bioavailability and reduction in dose,
cost effective manufacturing process, conventional
packaging due to exceptional durability and wide range
of doses (up to 200 mg of drug per unit)

Ing. and Tech. Used for Formulating FDT:

Drug

Disint.Agent
s

Other form. Ing.

Tech. used

Disint. Time

NSAIDS

Crospovidon
e
(intragranula
&
Extragranula
r)

Mcc,Aerosil,
Mag.
stearate, stearic
acid

Wet granulation &

Direct
Compression

50 sec
(for 125

Cross linked
povidone

Lemon flavor,
aspartame,
mannitol

Freeze drying

Avicel ph
101

Pregelatinized
starch,

Moulding, Direct
Compression

Sildenafil
granules

Ascorbic
acid

mgTab.)

< 30 sec

31-37 sec

Preformulation studies of ODT

Powder flow properties
Bulk Density (Db)
Tapped Density (Dt)
Angle of Repose
Carrs index (or) % compressibility
Hausner ratio

Evaluation test for ODT

General Appearance
Hardness
Drug Content
In-Vitro drug release
Modified disintegration
test
Moisture uptake study

Weight variation
Friability (F)
Wetting time & Water
absorption Ratio
Powder X-ray diffraction
In-vitro dispersion time
Stability study

Wetting time and water absorption ratio

Wetting time of dosage form is related to
with the contact angle.
Wetting time of the ODT is another
important parameter, which needs to be
assessed to give an insight into the
disintegration properties of the tablet.
Lower wetting time implies a quicker
disintegration of the tablet.

 The wetting time of the tablets can be measured by

using the simple procedure.[29] Five circular tissue
papers of 10cm diameter are placed in a petridish. Ten
milliliters of water soluble dye solution 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 the wetting time.

water absorption ratio

The weight of the tablet before keeping in
the petridish is noted (Wb)
The wetted tablet from the petridish is
taken and reweighed (Wa)
The water absorption ratio, R can be the
determined according to the following
equation
R = 100 (Wa-Wb) / Wb

Disintegration test
The time for disintegration of ODTs is generally <1min
and actual the disintegration time that patients can
experience ranges from 5 to 30s
The standard procedure of performing disintegration test
for these dosage forms has several limitations and they
do not suffice the measurement of very short
disintegration times
The disintegration test for ODT should mimic
disintegration in mouth with in salivary contents

Modified disintegration test

The standard procedure of performing disintegration test for
these dosage forms has several limitations and they do not
suffice the measurement of very short disintegration times.
The disintegration time for ODT needs to be modified as
disintegration is required without water, thus the test should
mimic disintegration in salivary contents.
For this purpose, a petridish (10 cm diameter) was filled with
10 ml of water.
The tablet was carefully put in the center of petridish and the
time for the tablet to completely disintegrate into fine particles
was noted.

Dissolution test
Commonly the drugs may have dissolution conditions as
in USP monograph
Other media such as 0.1 N HCl, pH 4.5 and pH 6.8
buffers should be used for evaluation of ODT in the
same way as their ordinary tablet counterparts
Experience has indicated that USP 2 paddle apparatus
is most suitable and common choice for dissolution test
of ODT tablets, where a paddle speed of 50 rpm is
commonly used
Typically the dissolution of ODTs is very fast when using
USP monograph conditions
Hence slower paddle speeds may be utilized to obtain a
comparative profile.

Patient counseling points for ODT

Patients may mistake ODT for effervescent tablets,
pharmacist need to be clearly told about the different
between them
ODT need to be handled carefully because some of ODT
developed may not have sufficient mechanical strength
Patients with dryness of mouth or with siogrens
syndrome or who taking anticholengic drugs may not be
suitable population for administering ODT.
Although no water is needed to allow the drug to dispense
quickly and efficiently but most technologies of ODT utilizes the
body own salivation but decreased volume of saliva may slow
down dissolution/ disintegration/ bioavailability of the product

 Although chewable tablets have been in the market for

long time, patients need to be counseled properly the
difference between chewable and ODT tablets
ODT can be used easily in children who have lost their primary
teeth but do not have full use of their permanent teeth and also
for geriatric patients who have lost their teeth permanently.

TERIMAKASIH