ORAL DISINTEGRATING TABLETS

Agus Siswanto
 Introduction
• Oral routes of drug administration have wide
acceptance up to 50-60% of total dosage forms
• tablets that can rapidly dissolve or disintegrate in
the oral cavity have attracted a great deal of
attention
– in the case of the motion sickness (kinetosis) and
sudden episodes of coughing during the common
cold, allergic condition and bronchitis
– People who have swallowing difficulties, but also are
ideal for active people
 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)
• Fast dissolving tablets, mouth-dissolving tablets, melt-
in mouth tablets, Orodispersible tablets, rapimelts,
porous tablets, quick dissolving
 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
• Drug should have good stability in saliva and
water
 Unsuitable drug candidate for orally
disintegrating tablet should include:
• Short half life & frequent dosing drugs
• Very bitter or unacceptable taste & odor drugs
 Advantages of ODT
• Improved patient compliance
• Rapid onset of action and may offer an improved
bioavailability (insoluble & hydrophobic drugs)
• Useful for pediatric, geriatric and psychiatric
patients
• Suitable during traveling where water is may not
be available
• Smooth mouth feel and pleasant taste
• Good chemical stability as conventional oral solid
dosage form
 Characteristics of an Ideal ODT
• Require no water for oral administration
• Dissolve / 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 (low cost)
 Basic approaches to develop
Oral Disintegrating Tablets
porous structure

highly water-soluble appropriate disintegrating

excipients agents
 Techniques in preparation of ODT
1. Freeze drying / lyophilization
2. Tablet Moulding
3. Spray drying
4. Sublimation
5. Direct compression
6. Mass extrusion
 1. 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 → can dissolve
rapidly
• 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
 2. Tablet Moulding
• Water-soluble ingredients with a hydro-
alcoholic solvent is used and is molded
into tablets under pressure lower than that
used in conventional tablet compression

• Molded tablets are very less compact than

compressed tablet porous structure that
enhances disintegration/ dissolution and
finally absorption increased
 3. Spray drying
• 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
• Formulation
– bulking agent → mannitol or lactose
– superdisintegrants→ sodium starch glycolate or
crosscarmellose or crospovidone
– acidic ingredient (citric acid) and/or alkaline ingredients
(e.g. sodium bicarbonate)
• This spray-dried powder → compressed into tablets
• Ex. Hyoscyamine Sulfate ODT
“Spray drying”
 4. Sublimation
• This technique is based on the use of volatile
ingredients to other tablet excipients and the
mixture is then compressed into tablets
– (e.g. camphor, ammonium bicarbonate,
naphthalene, urea, urethane)
• Entrapped volatile material is then removed
via sublimation, which leads to formation of a
porous structure
• Usually disintegrate in 10-20 sec
Steps Involved in sublimation
 5. Mass-Extrusion
• Involves softening the active blend using the solvent
mixture of water soluble (polyethylene glycol,
methanol)

• 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
 6. Direct compression
• This is most popular technique because of its
easy implementation and cost-effectiveness
– Direct compression represents the simplest & most
cost effective tablet manufacturing technique
• Can be applied to preparation of ODT because of
the availability of improved excipients especially
superdisintegrants & sugar based excipients
• The basic principle involves addition of
disintegrants and/or water soluble excipients
and/or effervescent agents
• Superdisintegrants (2- 5%) → to achieve rapid
disintegration along with the good mouth feel
MANUFACTURING STEPS FOR DIRECT COMPRESSION
 (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. Porosity & 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 → melemahkan intermolecular
bond → breaks the tablet into fine particles
• Water uptake by tablet depends upon hydrophilicity of
the drug /excipient
• For these types of disintegrants maintenance of porous
structure and low interfacial tension towards aqueous
fluid → by creating a hydrophilic network around the
drug particles
 2. Swelling
• General mechanism of action for tablet
disintegration
• Sufficient swelling force is exerted in the
tablet with low porosity
• if the packing fraction is very high → fluid is
unable to penetrate in the tablet and
disintegration is again slows down → dibuat
low porosity dg mekanisme sweeling
 3. Due to disintegrating
particle/particle repulsive forces
• Another mechanism of disintegrant 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 → these deformed
particles get into their normal structure when
they come in contact with aqueous media or
water
• 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
 (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,
• 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
– low mouldability but high dissolution rate
– lactose and mannitol
• Type 2 saccharides
– high mouldability and low dissolution rate
– maltose and maltilol
 Ing. and Tech. Used for Formulating FDT:
Drug Disint.Agents Other form. Ing. Tech. used Disint. Time

NSAIDS Crospovidone Mcc,Aerosil, Mag. Wet granulation & Direct 50 sec

(intragranula stearate, stearic Compression
& acid (for 125 mgTab.)
Extragranular)

Sildenafil Cross linked Lemon flavor, Freeze drying

povidone aspartame, < 30 sec
granules
mannitol

Ascorbic Avicel ph 101 Pregelatinized Moulding, Direct

acid starch, 31-37 sec
Compression
List of commercially Available Fast dissolving tablets
 Preformulation studies of ODT
Powder flow properties
• Bulk Density (Db)
• Tapped Density (Dt)
• Angle of Repose (< 30°)
• Carr’s index (or) % compressibility (<
20%)
• Hausner ratio (< 1,25)
 Evaluation test for ODT
• General Appearance • Weight variation
• Hardness • Friability (F)
• Drug Content • Wetting time & Water
• In-Vitro drug release absorption Ratio
• Modified disintegration • Powder X-ray diffraction
test • In-vitro dispersion time
• Moisture uptake study • Stability study
 Wetting time & water absorption ratio

• important parameter → needs to be

assessed to give an insight into the
disintegration properties of the tablet

• Lower wetting time → a quicker

disintegration of the tablet
 The wetting time of the tablets can be
measured by using the simple procedure

• Five circular tissue papers of 10 cm 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

R = 100 (Wa-Wb) / Wb

• The weight of the tablet before keeping in

the petridish is noted (Wb)
• The wetted tablet from the petridish is
taken and reweighed (Wa)
 Disintegration test
• The time for disintegration of ODTs
– generally < 1 min
– actual the disintegration time that patients can
experience ranges from 5 to 30s
• Uji waktu hancur tablet konvensional?
– 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
• A petridish (10 cm diameter) was filled with 10
ml of water
• The tablet was carefully put in the center of
petridish
• the time for the tablet to completely disintegrate
into fine particles was noted
 Dissolution test
• USP monograph
• Medium → 0.1 N HCl, pH 4.5 and pH 6.8 buffers
• USP 2 paddle apparatus
– 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
• Syarat disolusi sesuai monografi sediaan dalam
kompendia (misal FI atau USP)
– Misal C45 piroksikam > 75 %
TERIMAKASIH