Orally disintegrating tablets 1

1. Orally Disintegrating Tablets
“A Review”

2. ODTs……?
 Solid unit dosage forms
 Disintegrate / dissolve (secs.) in buccal cavity
 Do not require water for intake
ODTs are also called mouth-dissolving tablets (MDTs),
quick-dissolve, fast-melt, fast dissolving tablets (FDTs) and
rapid-disintegrating tablets (RDTs) and freeze-dried wafers.

3. Official definitions;
 USFDA-CDER:
“A solid dosage form containing medicinal substances, which
disintegrates rapidly, usually within a matter of seconds, when
placed upon the tongue".
 European Pharmacopoeia:
“Uncoated tablet that can be placed in the mouth where it disperses
rapidly before swallowing”.

4. Advantages:
 Ease of administration to patients who cannot swallow,
such as the elderly, stroke victims and bedridden patients.
 Accurate dosing as compared to liquid formulations.
 More rapid drug absorption from the pre-gastric area i.e.
mouth, pharynx and esophagus which may produce rapid
onset of action.
Limitations:
 Limited amount of drug can be incorporated in unit dose.
 Its difficult to take bitter drugs as ODTs.
 ODTs can not provide controlled or sustained release.

5. An ideal ODT should…!!
 not require water to swallow and should dissolve or disintegrate in the
mouth within a few seconds.
 allow high drug loading.
 be compatible with taste masking and other excipients.
 have a pleasing mouth feel.
 leave minimal or no residue in the mouth after oral administration.
 have sufficient strength to withstand the rigors of the manufacturing
process and post manufacturing handling.
 exhibit low sensitivity to environmental conditions such as humidity and
temperature.
 be adaptable and amenable to existing processing and packaging
machinery.
 cost effective.

6. Right candidate for ODTs….?
 no bitter taste
 dose lower than 20 mg
 small to moderate molecular weight
 good solubility in water and saliva
 partially non-ionized at the oral cavity's pH (6.8)
 ability to diffuse and partition into the epithelium of the upper GIT
 ability to permeate oral mucosal tissue.

7. Taste masking methods
 Use of flavour and sweetners.
 Polymer coating on drug particles e.g. Hydroxy propyl methyl
cellulose, Ethyl cellulose, Methacrylates, Kollicoat, Polyvinyl
pyrollidone
 Use of Cyclodextrins to form inclusion complex with drug
molecules. It also add in solubilzation of many drugs. The
suppression of bitter taste by cyclodextrin was in increasing order of
alpha, gamma, beta cyclodextrin.
 Drug complexation with resinates (ion exchange resins) which do
not release drug at salivary pH e.g.

8. Bitter Drugs masked by ion exchange resin
Drug Ion exchange resin
Norfloxacin Indion 204 (weak cation exchange resin)
Ciprofloxacin Indion 234 (weak cation exchange resin)
Roxithromycin Indion 204 (weak cation exchange resin)
Chloroquine phosphate Indion 234 (weak cation exchange resin)
Other examples :
Amberlite IR 120, Amberlite IRP 69, Amberlite IRC 50, Amberlite IRP88, Amberlite
IR 400, Amberlite IR 4B
Dowex 50, Dowex 1, Dowex 2
Indion 244, Indion 254, Indion 204, Indion 234, Indion 454
Tulsion T-344, Tulsion T-335, Tulsion T-339
Duolite AP 143

9. Preparation of ODTs
 Lyophilization
 Tablet Molding
 Sublimation
 Compression method
Lyophillzation
The drug is dissolved / dispersed in an aqueous solution of a
carrier/polymer. The mixture is dosed by weight and poured in the
wells of the preformed blisters. These blisters are then freez dried.
After freeze-drying the aluminium foil backing is applied on a blister-
sealing machine.
The major disadvantages of lyophillization technique are that it is
expensive and time consuming.

10. Tablet Molding
1. Solvent method
Moistening of powder blend (containing drug) with a
hydro-alcoholic solvent followed by compression at low pressures
in molded plates to form a wetted mass. The solvent is than
removed by air-drying.
2. Heat method
It involves preparation of suspension of drug blend in
heated agar solution, which is poured into preformed blisters &
solidified at RT. Dried at 30˚C under vacuum.

11. Sublimation
Highly volatile ingredients like benzoic acid, camphor, naphthalene,
urea, urethane and phthalic anhydride may be compressed along
with other excipients into a tablet.
This volatile material is then removed by sublimation leaving
behind a highly porous matrix.

12. Compression method
 Simplest and most cost effective technique.
 Use of conventional tablet excipients, manufacturing and packaging
machinery.
 Disintegration is achieved by following approaches;
1. Use of disintegrants e.g. SSG, Crospovidone, Cross Carmellose
Sodium etc. Can also be used with wet granulation technique.
2. Use of effervescent agents (ORASOLV) e.g. Sodium bi-carbonate,
sodium carbonate etc.
3. Use of Sugar based excipients (WOWTAB) e.g. dextrose, fructose,
isomalt, lactitol, maltitol, maltose, mannitol, sorbitol, starch
hydrolysate, polydextrose and xylitol.

13. CHARACTERIZATION
 Weight variation
 Content uniformity
 Hardness
Wetting time
Five circular tissue papers of 10 cm diameter are placed in a
petridish with a 10 cm diameter. 10 ml of water-containing Eosin, a
water-soluble dye, is added to petridish. A tablet is carefully placed
on the surface of the tissue paper. The time required for water to
reach upper surface of the tablet is noted as a wetting time.
Friability
Thickness
Dissolution

14. Disintegration of ODTs
European Pharmacopoeia: 5th edition, 2004:
 ODTs disintegrate within 3 min. when examined by the test for
disintegration of tablets & capsules.
USFDA-CDER:
 This practice is under review
 General recommandations for ODTs;
 Disintegration time upto 30 secs. (USP disintegration test
method)
 Weight of tablets upto 500 mg

15. Marketed Formulations
First ODT, received USFDA approval, Claritin (loratadine) in Dec’1996
Product Manufactured By/For Active ingredient
Alavert Quick Dissolving Tablets Wyeth Loratadine
Allegra ODT Sanofi Aventis Fexofenadine
Benadryl FastMelt Pfizer Diphenhydramine
Claritin RediTabs Schering-Plough Loratadine
Loratadine Redidose Ranbaxy Loratadine
Maxalt-MLT Merck & Co. Rizatriptan
Ondansetron ODT Teva Pharmaceuticals Ondansetron
Zofran ODT GlaxoSmithKline Ondansetron
Zomig-ZMT AstraZeneca Zolmitriptan
Zyprexa Zydis Eli Lilly and Company Olanzapine