This document provides an overview of orally disintegrating tablets (ODTs), including: 1. The definition and ideal properties of ODTs according to regulatory agencies. 2. The large market potential and growth of ODTs globally, especially for drugs treating central nervous system and gastrointestinal conditions. 3. Important patented technologies for developing ODTs, such as Zydis® technology which uses a lyophilization process to create a porous structure for rapid disintegration. 4. Common excipients and formulation methods used in ODTs, including lyophilization, molding, and mass extrusion.

1. 1

2. CONTENTS
Introduction
Market potential of ORAL DISPERSIBLE TABLETS’s
Ideal properties, advantages & disadvantages
Mechanisms of ODT’s
Formulation of ODT’s
Excipients used in ODT’s preparation
Conventional techniques for preparing ODT’s
Important patented technologies of ODT’s
Evaluation of ODT’s
Patents of ODT’s
Conclusion
References
2

3. INTRODUCTION
United States Food and Drug
Administration (FDA) Center for Drug
Evaluation and Research (CDER)
define orally disintegrating tablets in the
‘Orange Book’ as
“A solid dosage form which contain a medicinal
substance or active ingredient which
disintegrates rapidly within a matter of
seconds when placed upon a tongue” .
European Pharmacopoeia described orally
disintegrating tablets as “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”.
3

4. 2009
2015
2025
6 BILLION
13 BILLION
27 BILLION
2009 2015 2025
0
5
10
15
20
25
30
MARKET POTENTIAL FOR ODT$USDOLLARS
TIME IN YEARS
C.A.G.R
11.5%
4
Orally Disintegrating Tablet in Global market, especially in North America,
China, Europe, Southeast Asia, Japan and India,

5. CENTRAL NERVOUS SYSTEM
GASTRO INTESTINAL
ONCOLOGY
OTHERS
THE GLOBAL MARKET CATEGORY IN ODT’s
OTHERS (67%)
Anti-Psychotics (20% )
Anti-Epileptics (13%)
5

6. ORAL
DISPERSIBLE
TABLETS
MELT-IN-MOUTH
TABLETS
REPIMELTS
FREEZE-DRIED
WAFERS
FAST-MELTING
TABLETS
MOUTH-
DISSOLVING
TABLETS
RAPID
DISINTEGRATING
TABLET
6

7. DISINTEGRATES
WITHOUT
WATER
LEAVE
NEGLIGIBLE OR
NO RESIDUE IN
THE MOUTH
COMPATIBLE
WITH
EXCIPIENTS
INSENSITIVE TO
ENVIRONMENT
CONDITIONS
MOUTH FEEL
SHOULD BE
PLEASANT
MUST HAVE
SUFFICIENT
STRENGTH
ORAL
DISPERSIBLE
TABLET
IDEAL PROPERTIES OF ODTs
7
Thakur, R.R. and Kashi, M., 2011. An unlimited scope for novel formulations as orally
disintegrating systems: Present and future prospects

8. ADVANTAGES OF ODT’s
•Enhanced oral absorption
•Rapid onset of action
•Minimized first pass effect
•High bioavailability
•Rapid disintegration
•Improved taste
•Age specific formulation
(pediatric,
geriatric patient)
•Improved patient compliance
•Suitable during traveling
where water may not be available
8

9. Insufficient
Mechanical Strength
Unpleasant Taste Or
Grittiness
Requires Special
Packaging
Hygroscopic
Larger Doses Are
Difficult To Formulate
DISADVANTAGES OF ODT’s
9
Chotaliya, M.B. and Chakraborty, S., 2012. Overview of oral dispersible tablets. International Journal of
PharmTech Research, 4(4), pp.1712-20.

10. Fast dissolving granules
MECHANISM OF ODT DISINTEGRATION
Major mechanism of ODT are : DRUG
Disintegrating Agent
Saliva in mouth causes
disintegrating agent to
swell creating channels
for saliva
Fast dissolving granules
dissolves and tablet
disintegrate
WICKING
ENZYMATIC
REACTION
SWELLING
CHEMICAL
REACTION
PARTICLE
REPULSIVE
FORCE
DEFORMATION
10
Brahmaiah . Formulation and evaluation of orodispersable Atenolol Maleate Tablets: A Comparative Study
on Natural Super disintegrents and Synthetic disintegrents. IJoR in Ayurveda and Pharmacy, 5(2), pp.185-
192.

11. FORMULATION OF ODT’S
11

12. TASTE
DOSE
STABILITY
pKA
UNDESIRED
SHOULD NOT HAVE
BITTER TASTE
DOSE SHOULD BE LESS
THAN 20 mg
Should have good
stability in water and
saliva
Unionised at oral
cavity
Short half life drugs
Should able to
penetrate oral mucosa
Drug requiring
frequent dosing
CRITERIA FOR SELECTION OF DRUG
12

13. CATEGORY ACTIVE INGREDIENT
Antiasthmatic Montelukast Sodium
Anticoagulants Dicoumarol, Dipyridamole, Nicoumalone, Phenindione
Antidiabetics Glipizide, Tolbutamide, Glibenclamide, Tolazamide, Gliclazide,
Chlorpropamide.
Antigout Agents Allopurinol, Probenecid, Sulphinpyrazone.
Antihypertensive Amlodipine Beyslate, Carvedilol, Benidipine, Darodipine, Dilitazem,
Diazoxide, Felodipine, Guanabenz Acetate, Indoramin, Isradipine, Minoxidil,
Antihistamines Loratadine, Cetrizine HCl, Cinnarizine, Triprolidine, Fexofenadine.
Antiepileptics Beclamide, Carbamazepine, Clonazepam, Ethotoin, Methoin, Methsuximide,
Methylphenobarbitone, Phenacemide, Phenobarbitone, Phenytoin,
Phensuximide, Primidone, Sulthiame, Valproic Acid.
Antiarrhythmics Flecainide Acetate, Quinidine Sulphate, Amiodarone HCl, Disopyramide.
Analgesics and
Antiinflammatory
Agents
Azapropazone, Benorylate, Diflunisal, Etodolac, Fenbufen, Fenoprofen
Calcim, Flurbiprofen, Ibuprofen, Indomethacin, Ketoprofen, Paracetamol.
Antibacterial
Agents
Benethamine Penicillin, Cinoxacin, Ciprofloxacin, Clarithromycin,
Clofazimine, Cloxacillin Sodium, Demeclocycline, Doxycycline, Erythromycin,
Ethionamide, Imipenem, Nalidixic Acid, Nitrofurantoin, Nalidixicacid,
Rifampicin, Spiramycin, Sulphabenzamide, Sulphadoxine.
Antidepressants Amoxapine, Ciclazindol, Maprotiline, Mianserin, Nortriptyline, Trazodone
Anticonvulsant Lamotrigine
Antifungal Agents Amphotericin, Clotrimazole, Econazole Nitrate, Fluconazole, Fiucytosine,
Griseofulvin, Itraconazole, Ketoconazole, Miconazole, Natamycin, Nystatin,
Sulconazole Nitrate, Terbinafine, Terconazole, Tioconazole, UndecenoicAcid
Antihelmintics Albendazole, Bephenium Hydroxynaphthoate, Cambendazole,
Dichlorophen, Livermectin, Pyrantel Embonate, Thiabendazole
13

14. Antimalarials Amodiaquine, Chloroquine, Chlorproguanil, Halofantrine, Mefloquine,
Proguanil, Pyrimethamine, Quinine Sulphate.
Antimigraine Agents Dihydroergotamine Mesylate, Ergotamine Tartrate, Methysergide Maleate,
Pizotifen Maleate, Sumatriptan Succinate, Rizatriptan Benzoate, Diclofenac
Potassium
Antineoplastic Agents
And
Immunosuppressants
Aminoglutethimide, Amsacrine, Azathioprine, Busulphan, Chlorambucil,
Cyclosporin, Dacarbazine, Estramustine, Etoposide, Lomustine, Melphalan,
Mercaptopurine, Methotrexate, Mitomycin, Mitotane, Mitozantrone,
Procarbazine, Tamoxifen Citrate, Testolactone
Antiprotozoal Agents Benznidazole, Clioquinol, Decoquinate, Diiodohydroxyquinoline, Diloxanide
Furoate, Dinitolmide, Furzolidone, Metronidazole, Nimorazole,
Nitrofurazone, Omidazole, Tinidazole
Antiparkinsonian Agents Bromocriptine Mesylate, Lysuride Maleate, Selegiline
Antithyroid Agents Carbimazole, Propylthiouracil
Local Anaesthetics Lidocaine
Neuromuscular Agents Pyridostigmine.
Cardiac Inotropic Agents Amrinone, Digitoxin, Digoxin, Enoximone, Lanatoside C, Medigoxin
Corticosteroids Beclomethasone, Betamethasone, Budesonide, Cortisone Acetate,
Desoxymethasone, Dexamethasone, Fludrocortisone Acetate, Flunisolide,
Flucortolone, Fluticasone Propionate, Hydrocortisone,
Methylprednisolone, Prednisolone, Prednisone, Triamcinolone
Nutritional Agents Betacarotene, Vitamin A, Vitamin B2 , Vitamin D, Vitamin E, Vitamin K,
VitaminC
Opioid Analgesics Codeine, Dextropropyoxyphene, Diamorphine, Dihydrocodeine,
Meptazinol, Methadone, Morphine, Nalbuphine, Pentazocine
14

15. Oral Vaccines
Vaccines for Influenza, Tuberculosis, Meningitis, Hepatitis, Whooping Cough, Polio,
Tetanus, Diphtheria, Malaria, Cholera, Herpes, Typhoid, Hiv, Aids, Measles, Lyme
Disease, Travellers Diarrhea, Hepatitis A, B And C, Otitis Media, Dengue Fever,
Rabies, Parainfluenza, Rubella, Yellow Fever, Dysentery, Legionnaires Disease,
Toxoplasmosis, Q-Fever, Haemorrhegic Fever, Argentina Haemorrhagic Fever,
Caries, Chagas Disease, Pneumoccoccal Disease, Mumps
Proteins, Peptides And
Recombinant Drugs
Insulin, Glucagon, Somatotropin, Calcitonins, Enkephalins, Interferons
Stimulants Amphetamine, Dexamphetamine, Dexfenfluramine, Fenfluramine, Mazindol,
Pemoline
Sex Hormones Clomiphene Citrate, Danazol, Ethinyloestradiol, Medroxyprogesterone Acetate,
Mestranol, Methyltestosterone, Norethisterone, Norgestrel, Oestradiol,
Conjugated Oestrogens, Progesterone, Stanozolol, Stiboestrol, Testosterone,
Tibolone
15

16. 16

17. EXCIPIENTS EXAMPLES
Super-disintegrants Crosscarmellose®, Ac-Di-Sol®, Primellose®, Vivasol,
Crosspovidone, Soya polysaccharides
Binder Povidones, polyvinyl alcohols, acrylic polymers, hydroxyl propyl
cellulose
Saliva stimulating agent Citric acid, malic acid, tartaric acid, ascorbic acid and lactic acid
Antistatic agents Sodiumlaurylsulfate, polyoxyethylene sorbitan fatty acid esters
(Tweens), sorbitan fatty acid esters (Spans), polyoxyethylene
stearates
Flavouring agents Peppermint flavour, cooling flavor, flavor oils and flavoring
aromatic oil, vanilla, citrus oils
Sweetning agents Glucose, fructose, dextrose, sucrose, and
Isomaltose, sucralose(600–1000), neotame(2000–8000) 17
EXCIPIENTS:-

18. 18
Lyophilization V/S Direct compression
REFERENCE:- OFFICIAL SITE OF CATALENT PHARMA SOLUTION Published on Aug 17, 2015
https://www.youtube.com/watch?v=JsYGIe3Atxc

19. Freeze Drying/
Lyophilization
Moulding
Spray Drying
Mass Extrusion
Sublimation
Direct compression
Melt granulation
Cotton candy process
Phase transition
process
Zydis® Technology
Orasolv® Technology
Durasolv® Technology
Frosta® Technology
Wowtab® Technology
Flashtab® Technology
AdvaTab ® Technology
Nanocrystal®
Technology
Advantol®300
Industrial approaches
FOR ODT’s
CONVENTIONAL PATENTED
19

20. FREEZE DRYING / 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.
• useful for heat sensitive drugs i.e. thermo-labile substances
E.g-Loratidine (claritin reditapp )
20

21. MOLDING
• Tablets are prepared by using water-soluble ingredients
• The powder blend is moistened with a hydro alcoholic
solvent and is molded into tablets under pressure lower
than that used in conventional tablet
• Molded tablets are very less compact than compressed
tablets. these posses porous structure that increase
dissolution
• This technique is easy way to formulate odts since limited
number of processing steps
• Low manufacturing cost and also accommodate high dose the
final weight of tablet can easily exceed that of other production
method
E.g-zolmitriptan (zolmig repimelt)
Direct compression
21

22. SUBLIMATION
• Porosity is improved by using volatilizing agent.
• Volatile substances such as camphor can be used in tableting process, which get sublimated
from the formed tablet in vacuum at 80°c for 30 min after preparation of tablets.
• Presence of a highly porous structure in the tablet
• Matrix is the key factor for rapid disintegration of ODTs made by sublimation
Cotton candy process
• It utilizes a unique spinning mechanism to produce floss-like crystalline structure,
which mimics cotton candy (matrix of polysaccharides or saccharine )
• This candy flossmatrix is then milled and blended with active ingredients and
excipients and subsequently compressed to ODTs.
22

23. Mass Extrusion
• This technology 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 cylinder of
the product into even segments
• Finally cut into even segments using heated blade to form tablets.
E.g- Zolmitriptan ( Zolmig ZMT)
23

24. • 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
• Disintegrated within 20 seconds
E.g- Hyoscyamine sulphate ODT
Spray Drying
24

25. • Tablet produced by compressing the powder containing two sugar alcohols of
high and low melting point and subsequently heating at temperature between
their two melting points.
Phase transition process
ERYTHRITOL
(MP: 122 °c)
XYLITOL
(MP: 93-95 °c)
INTERPARTICULAR
BONDING
INCREASES
93 °C for 15 min
INCREASING IN
MEDIAN PORE
SIZE OF THE
TABLETS
Helps in faster disintegration of ODT’s
Increase in tablet hardness
25

26. PATENT TECHNOLOGY
• Lyophilizing the drug in a matrix
(gelatin).
• The product is very lightweight and
fragile and must be dispensed in a
special blister pack.
• In the freeze-dried product is too low
to allow for microbial growth
E.g Clartin Reditab® (loratidine), Feldene
(piroxicam)
Zydis® by R. P. Scherer Corporation
(Cardinal Health, Inc.) in SWEDEN
Flashtab ® Technology ® by
Ethypharm, Saint Cloud, France
• WET + DRY granulation before
compression.
• Relays on the use of super
disintegrates
E.g Nurofen® (ibuprofen)
26

27. Durasolv ® Technology by Cima Labs Inc
U.S.AOrasolv ® Technology by Cima Labs
Inc U.S.A
U.S.A
• Cima’s first orally disintegrating dosage
form.
• Direct compression of an effervescent
agent and taste masked drug.
• The use of effervescence causes a
tablet to disintegrate rapidly in less
than 1 min on contact with water or
saliva
E.g- orapred® (prednisolone),
flazaclo® (clozapine)
• DuraSolv is Cima's second-generation
fast disintegrating tablet formulation.
• DuraSolv has much higher mechanical
strength than Orasolv due to the use of
higher compaction pressures
• Tablets are highly durable
E.g- Nulev® (hyoscyamine sulphate)
27

28. WOW TAB ® Technology (Yamanouchi
Pharma, Inc. Japan)
Frosta ® Technology
(Akina )
• PLASTIC GRANULES  compression at
low pressure  produce strong tablets
with high porosity.
• Plastic granules = POROUS AND PLASTIC
material (Maltrin QD, Mannogem,) +
PENETRATION ENHANCER (Ethanol ,
Decanol)+ binder  WET GRANULATION
• Disintegration time - 15 to 30 sec
E.g- Fortecal® (bilastine)
• API CONSTITUTE OF 50% w/w
• Saccharides of both low and high
Moldability are used
• API are mixed with low Moldability
saccharides  granulated with high
Moldability saccharides Compression
• E.g- Gaster-D® (Famotidine)
28

29. AdvaTab ® (Eurand)
Advantol® Technology
(SPI pharma)
• Microencapsulation of API + gastro soluble
polymer.
• Mask the taste with restriction of drug
dissolution in mouth cavity.
• Disintegrate rapidly in the mouth, typically
in less than 30 seconds.
• E.g- Advatab CETRIZINE
• Requires no special manufacturing
equipment or tooling
• Formulations utilize a standard rotary
tablet press with standard tooling under
normal tableting temperature and
humidity conditions
• Reducing the production cycle time and
lowering costs
29

30. . Gavaskar, B., Kumar, S.V., Sharan, G., Nagaraju, M. and Rao,
Y.M., 2010. Present investigations and future prospects of
oral disintegrating tablets: A review. IJPSR, 1(8), pp.45-47.
OraQuick ® Technology
(KV Pharmaceutical Co., Inc.)
• Utilizes its own patented MicroMask®.
• MicroMask® dissolving the sugar (sucrose, mannitol,
sorbitol) + protein (albumin or gelatin) in suitable
solvent (ethanol, isoproryl alcohol )  solution is
spray dried  highly porous granules.
• Heat-sensitive drugs
30
Gavaskar, . Present investigations and future prospects of oral
disintegrating tablets: A review. IJPSR, 1(8), pp.45-47

31. 31
A- Clartin Reditab® (loratidine), B-Alavert ® (loratidine)
SEM pictures of horizontal cross section of oral
dispersible tablets
Fu, Y., Jeong, S.H. and Park, K., 2005. Fast-melting tablets based on highly plastic
granules. Journal of controlled release, 109(1), pp.203-210.

32. EVALUATION
General Appearance
Hardness / Crushing
strength
Weight variation
Thickness
Friability
Disintegration Time
Dissolution test
Water absorption
ratio
Wetting time
32

33. 33
Presently, neither USP nor the European Pharmacopoeia has defined a specific
disintegration test for ODTs.
The results from the USP disintegration test do not provide a strong correlation with in
vivo disintegration times in the mouth because the test uses a disintegration medium of
about 900 mL of water and a vigorously oscillating apparatus, which provide conditions
far than those found in vivo .
According to a test method reported in the 12th Annual FDA Science Forum , currently
there is no USP in vitro method for evaluating disintegration time for ODTs,
which represents in vivo disintegration time in the mouth. Therefore, FDA recommends
using a modified form of the USP disintegration test
Using a disposable syringe, 1 mL of water is delivered directly onto a tablet
placed on a flat surface. Completeness of disintegration of the tablet is checked
by the manual palpation of the tablet at the end of 30 s, which is set by FDA as
the disintegration specification for ODTs.
Park, J.H., Holman, K.M., Bish, G.A., Krieger, D.G., Ramlose, D.S., Herman, C.J.
and Wu, S.H., 2008. An alternative to the USP disintegration test for orally
disintegrating tablets. Pharmaceutical Technology, 32(8).

34. S.N0 Title Patent Number Year
1 Orally disintegrating tablet (Ticagrelor)
significant proportion of patients with stroke
have difficulty swallowing in the acute phase,
and many have ongoing problems.
WO2017182589 26.10.2017
2 Multilayered orally disintegrating tablets
containg drug unstable to light (Rosuvastatin)
An oral disintegrating tablet stable to light,
temperature and humidity can be provided by
preparing a multi-layered tablet containing
rosuvastatin
US20170231989 17.08.2017
3 Orally disintegrating tablet containing
(Asenapine)
treatment of adults with schizophrenia and acute
treatment of manic or mixed episodes associated
with bipolar I disorder with or without psychotic
features in adults
US20170143670 25.05.2017
RECENT PATENTS
34
http:patentscope.wipo.int/search

35. S.N0 Title Patent Number Year
4 Tofacitinib orally disintegrating tablets
use in moderate-to-severe forms of
rheumatoid arthritis. It helps to decrease pain,
tenderness, swelling in the joints.
WO2017017542 02.02.2017
5 Orally Disintegrating Tablet of (Nabilone)
Comprising Mannitol-Based Granules
Nabilone ODTs is used to treat severe nausea
and vomiting caused by cancer chemotherapy
US20170014340 19.01.2017
6 Orally disintegrating dosage form for administration
of (AVANAFIL), and associated methods of
manufacture and use
AVANAFIL ODT is used to treat impotence or
erectile dysfunction
US20160331687 17.11.2016
RECENT PATENTS
35
http:patentscope.wipo.int/search

36. Conclusion
ODT helps to overcome some of the problems that existed in
conventional solid dosage form i.e. difficulty in swallowing of tablet in
paediatric and geriatric patients who constitute a large proportion of
world's population.
ODT may lead to improve efficacy, bioavailability, rapid onset of
action, better patient compliance.
Oral dispersible tablet acts like solid dosage form when outside the
body and solution when administered.
Their characteristic advantages such as administration without water,
anywhere, anytime lead to their increased patient compliance in
today’s scenario of hectic life.
Considering the many benefits of ODTs, a number of formulations are
prepared in ODT forms, Because of increased patient demand, popularity
of these dosage forms will surely expand in future.
36

37. REFERENCES:
1. Gavaskar, B., Kumar, S.V., Sharan, G., Nagaraju, M. and Rao, Y.M., 2010. Present
investigations and future prospects of oral disintegrating tablets: A review. IJPSR,
1(8), pp.45-47.
2. Wagh, M.A., Kothawade, D.P., Salunkhe, K.S., Chavan, N.V. and Daga, V.R., 2010.
Techniques used in orally disintegrating drug delivery system. International journal
of drug delivery, 2(2).
3. Thakur, R.R. and Kashi, M., 2011. An unlimited scope for novel formulations as
orally disintegrating systems: Present and future prospects.
4. Chotaliya, M.B. and Chakraborty, S., 2012. Overview of oral dispersible tablets.
International Journal of PharmTech Research, 4(4), pp.1712-20.
5. Velmurugan, S. and Vinushitha, S., 2010. Oral disintegrating tablets: An overview.
International Journal of Chemical and Pharmaceutical Sciences, 1(2), pp.1-12.
6. Kuno, Y., Kojima, M., Ando, S. and Nakagami, H., 2005. Evaluation of rapidly
disintegrating tablets manufactured by phase transition of sugar alcohols. Journal
of controlled release, 105(1), pp.16-22.
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8. Pahwa, R. and Gupta, N., 2011. Superdisintegrants in the development of orally
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38. 9. Gohel, M., Patel, M., Amin, A., Agrawal, R., Dave, R. and Bariya, N., 2004.
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disintegrating tablet and patient counseling points for FDDTs-A Review.
11. Fu, Y., Jeong, S.H. and Park, K., 2005. Fast-melting tablets based on highly
plastic granules. Journal of controlled release, 109(1), pp.203-210.
12. Park, J.H., Holman, K.M., Bish, G.A., Krieger, D.G., Ramlose, D.S., Herman, C.J.
and Wu, S.H., 2008. An alternative to the USP disintegration test for orally
disintegrating tablets. Pharmaceutical Technology, 32(8).
38

39. 39