1. RESHMA VEMULA
MS. INDUSTRIAL
PHARMACEUTICS

2. o Introduction
o Objectives of The Study
o Review of literature
o Plan Of Work
o Materials & Methods:
• Pre-formulation
• Formulation &
• Evaluation
o References

4.  Def :-
Orally disintegrating tablets (ODTs) were defined as a solid dosage
form containing medicinal substances that disintegrate within a
matter of seconds when placed on tongue.
 According to EUROPEAN PHARMACOPEIA, ODTs were
defined as orodisperse that can be placed in mouth where it
disperses rapidly before swallowing.
 These are appropriate dosage form for older people, children, and
bedridden patients because it can be difficult for these patients to
swallow conventional tablets or capsules.
 In these patients, medication compliance and therapeutic effect
could be improved by taking ODTs that can rapidly and easily
disintegrate in oral cavity.

5. What are ODTs?
Solid dosage form
Rapid
Oral route of disintegration
administration on the tongue
Fast Dissolve
Dosage Form
A stable, oral dosage form
with the dosing ease of a liquid

6. Regulatory Definitions
US Definition
• Orally Disintegrating Tablet
• A solid dosage form containing medicinal substances which disintegrates
rapidly, usually within a matter of seconds when placed upon the tongue.
• Tablet weight <500mg. In-vitro USP disintegration test <30 seconds.
• FDA Guidance for Industry -Orally Disintegrating Tablets (Dec 2008)
EU Definition
• Orodispersible tablets
• Orodispersible tablets are uncoated tablets intended to be placed in the mouth
where they disperse rapidly before being swallowed
• Disintegration Test: Orodispersible tablets disintegrate within 3 mins when
examined by the test for disintegratioN.
• European Pharmacopoeia (Ph.Eur.)

7. Why use ODT?
ODT
• Clinical Formulation Marketing
• Pregastric delivery • Compliance • New presentation
• Faster onset • Convenience • Extend exclusivity
• Better S&E • Stability • Broader application
• Bioequivalence • Ease of use • USP
• Local delivery

8. CLASSIFICATION OF ODTs
First generation SECOND THIRD
ODTs generation ODTs generation ODTs
Preparation method • Prepared by freeze – • Wet granulation method • Dry granulation method
drying method. • Drying the drug and • Dry mass including the
• Drug suspension along additives after tabletting drug and saccharides were
with specific additives was their wet mass(TUSHIMA tabletted.
filled into the pockets of 2001).
press through packing.
ADVANTAGES • RAPID • Rapid disintegration of • Rapid disintegration of
DISINTEGRATION of ODTs ODTs
ODTs • Less friable then first
generation ODTs
DISADVANTAGES • Handling was difficult • LOW HARDNESS OF • High porosity
because the tablets were TABLETS • Low hardness
very friable • High porosity • Low density
• Highly sensitive to • Low density
moisture
• No Taste masking
compounds applied for
bitter tasting drugs
•Low density and hardness

9. Need for ODTs
 Orally disintegrating dosage forms are particularly suitable for patients
find it inconvenient to swallow traditional tablets and capsules with glass
of water.
 Pediatric and geriatric patients
 Patients who are unwilling to take solid preparation due to fear of
choking
 A patient with persistent nausea, who may be in journey, or has little or
no access to water
 Increased bioavailability and faster onset of action are a major claim of
these formulations.

10. Advantages of ODT’s
1. Good for patients with swallowing difficulties.
2. Good for paediatric compliance
3. Convenient to administer during travelling or working without need of water
4. The pre-gastric drug absorption avoids the first-pass metabolism.
5. Pregastric absorption leading to increased bioavaibility/ rapid absorption of drugs
from mouth, pharynx and oesophagus as saliva passes down to stomach, also
avoids hepatic Metabolism.
6. Convenient for administration to traveling patients and busy people who do not
have accesses to water.
7. Excellent mouths feel property produced by use of flavours and sweetners help to
change the perception of “medication as bitter pill” especially in pediatric
population.
8. Fast disintegration of tablets leads to quick dissolution and rapid absorption which
may produce rapid onset of action.
9. ODTs offer all the advantages of solid dosage forms and liquid dosage forms.
10. Convenience of administration and accurate dosing compared to liquids.

11. Drug selection criteria
The ideal characteristics of a drug for oral dispersible tablet include:
 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 50mg.
 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.

12. IMPORTANT CRITERIA FOR EXCIPIENTS USED IN THE
FORMULATION OF ODTs:
• It must be able to disintegrate quickly.
• Their individual properties should not affect the ODTs.
• It should not have any interactions with drug and other excipients.
• It should not interfere in the efficacy and organoleptic properties of the product.
• When selecting binder a (single or combination of binders) care must be taken in the
final integrity and stability of the product.
• The binders may be in liquid, semi liquid, solid or polymeric mixtures11.
(Ex: Polyethylene glycol, coca butter, hydrogenated vegetable oils)

13. Formulation of ODT’s
• Active ingredient
• Disintegrating agents
• Binders
• Sweeteners
• Flavoring agents
• Glidants, lubricants, anti-adherents.

14. Formulation of ODT’s
Disintegrating agents:
 Starch and modified starches (e.g. – Primogel, Carboxy methyl Starches,
Pregelatinized, Starch USP, Starch 1500 )
 Cross-linked polyvinylpyrrolidone (eg. Povidone).
 Modified celluloses such as cross-linked sodium carboxymethylcellulose
(eg. Ac-Di-Sol)
 Alginic acid and sodium alginate
 Microcrystalline cellulose e.g. - Avicel DG, Avicel PH-101.
 Super disintegrants - Crosscarmellose®
Ac-Di-Sol® Swelling is in two dimensions.
-Direct compression or granulation
Primellose® -Starch free
Vivasol®
Water insoluble and spongy in
Crosspovidone - nature so get porous tablet
Sodium Starch Glycolate -
Soy polysaccharides Rapid dissolving.
Emcosoy Does not contain any starch or
sugar. Used in nutritional products.

15. Formulation of ODT’s
Binders :
SMCC (Silicified microcrystalline cellulose )
SMCC1 SMCC2 SMCC3
Starch paste , Natural Gums, Liquid Glucose , etc. )
Flavors:
A bitter product - mint, cherry or anise may be used
A salty product – peach, apricot or liquorice may be used
A sour product - raspberry or liquorice may be used
An excessively sweet product - vanilla may be used

16. TECHNOLOGIES FOR PREPARING ODT’S
The various technologies adopted to prepare ODTs are:
a)Freeze drying / Lyophilization
b)Moulding
c)Sublimation
d)Spray drying
e)Mass extrusion
f)Direct compression

17. Direct compression
• Easiest way to manufacture tablets is direct compression
.
• Low manufacturing cost, conventional equipments and limited number of processing steps led
this technique to be a preferable one. However disintegration and dissolution of directly
compressed tablets depend on single or combined effect of disintegrant, water soluble
excipients
and effervescing agents.
• It is essential to choose a suitable and an optimum concentration of disintegrant to ensure quick
disintegration and dissolution.
• Superdisintegrants are newer substances which are more effective at lower concentrations with
greater disintegrating efficiency and mechanical strength.
• On contact with water, the superdisintegrants swell, hydrate, change volume or form and
produce a disruptive change in the tablet. Effective superdisintegrants provide improved
compressibility, compatibility and have no negative impact on the mechanical strength of
formulations containing high dose drugs.

18. • The type of disintegrants and its proportion are of prime importance.
• Also factors to be considered are particle size distribution, contact angle, pore size distribution
and water absorption capacity.
• Studies revealed that the water insoluble superdisintegrants like sodium starch glycolate and
Croscarmellose sodium show better disintegration property than the slightly water soluble
agents like Crospovidone, since they do not have a tendency to swell.
• Superdisintegrants that tend to swell show slight retardation of the disintegration property due
to formation of viscous barrier. There is no particular upper limit regarding the amount of
superdisintegrant as long as the mechanical properties of the tablet are compatible with its
intended use. The superdisintegrant may be used alone or in combination with other
superdisintegrants.

19.  Freeze Drying
A process in which water is sublimated from the product after freezing.
Lyophilization is a pharmaceutical technology which allows drying of heat sensitive
drugs and biological at low temperature under conditions that allow removal of water
by sublimation.
Lyophilization results in preparations, which are highly porous, with a very high
specific surface area, which dissolve rapidly and show improved absorption and
bioavailability.
 Moulding
In this method, molded tablets are prepared by using water-soluble ingredients so that
the tablets dissolve completely and rapidly.
The powder blend is moistened with a hydro-alcoholic solvent and is molded into
tablets under pressure lower than that used in conventional tablet compression.
The solvent is then removed by air-drying. Molded tablets are very less compact than
compressed tablets. These possess porous structure that enhances dissolution.

20. • Sublimation
The slow dissolution of the compressed tablet containing even highly water-
soluble ingredients is due to the low porosity of the tablets. Inert solid
ingredients that volatilize readily (e.g. urea, ammonium carbonate,
ammonium bicarbonate, camphor etc.) were added to the other tablet
ingredients and the mixture is compressed into tablets.
The volatile materials were then removed via sublimation, which generates
porous structures.
Additionally, several solvents (e.g. cyclohexane, benzene) can be also used
as pore forming agents.

21. Patented Technologies For Fast Dissolving
Tablets
Zydis Technology
A Zydis tablet is produced by lyophilizing or freeze-drying the drug in a matrix
usually consisting of gelatin.
The product is very lightweight and fragile, and must be dispensed in a special
blister pack.
Patients should be advised not to push the tablets through the foil film, but instead
peel the film back to release the tablet.
The Zydis product is made to dissolve on the tongue in
2 to 3 seconds.
Feldene Melt (Piroxicam 20 mg )
Claritin Reditab (Loratidine 10 mg )

22. • Durasolv Technology
The tablets made by this technology consist of a drug, fillers and a
lubricant.
Tablets are prepared by using conventional tableting equipment and
have good rigidity.
These can be packed into conventional packaging system like blisters.
Durasolv is an appropriate technology for products requiring low
amounts of active ingredients.
Parcopa® (levodopa and carbidopa)
NuLev® (hyoscyamine)
• Orasolv Technology
In this system active medicament is taste masked.
It also contains effervescent disintegrating agent.
Tablets are made by direct compression technique at low compression
force in order to minimize oral dissolution time.
Conventional blenders and tablet machine is used to produce the tablets.
The tablets produced are soft and friable and packaged in specially
designed pick and place system.
FazaClo® (clozapine)
Orapred ODT®** (prednisolone sodium phosphate)

23. Drugs Formulated Into ODT’s
• Analgesics and Anti-inflammatory Agents:
e.g. Azapropazone, Meclofenamic Acid, Indomethacin, Phenylbutazone,
etc.
• Anthelmintics
e.g. Albendazole, Mebendazole, Dichlorophen, etc.
• Anti-coagulants:
e.g.Dicoumarol, Nicoumalone, Phenindione, etc.
• Anti-bacterial Agents:
e.g. Penicillin, Ciprofloxacin, Clarithromycin, Clofazimine, Cloxacillin,
Demeclocycline, Doxycycline, Erythromycin, Ethionamide,

24. • Anti-Epileptics:
e.g. Carbamazepine, Clonazepam, Ethotoin, Methoin, etc.
• Anti-Fungal Agents:
e.g. Amphotericin, Clotrimazole, Econazole Nitrate, Fluconazole,
Fiucytosine, Griseofulvin, Itraconazole, Ketoconazole, Miconazole,
Natamycin, Nystatin. Etc.

25. • Formulation and evaluation of oral disintegrating tablets of Sertraline :
Suhas M. Kakade1*, Vinod S. Mannur1,Ravindra V. Kardi1, Ketan B. Ramani1, Ayaz A. Dhada11, Department of
Pharmaceutics, K.L.E. University’s college of pharmacy, J.N.M.C. Campus, Belgaum – 590010, India.
Orally disintegrating tablets prepared by direct compression and using super disintegrants like
crospovidone, croscarmellose sodium and sodium starch glycolate designate, designated as three different
groups of formulation ( A, B and C) respectively were prepared and evaluated for the pre-compression
parameters such as bulk density, compressibility, angle of repose etc.
• Formulation and evaluation of oral disintegrating tablets of Ondasetron hydrochloride
using natural superdisintegrants:
Nitin Bansal*, Govind Sharma, College of Pharmacy, IPS Academy, Indore (M. P.),India.
Tablets containing the drug were prepared by dry granulation method using different concentrations of
superdisintegrants such as modified gum karaya, modified natural agar, crosscarmellose sodium and sodium
starch glycollate. The formulations were evaluated for weight variation, hardness, friability, drug content,
wetting time, in vitro disintegration time and in vitro dissolution study.
• Formulation and evaluation of oral disintegrating tablets of Salbutamol sulphate by cost-efficient |
direct compression method :
Reeta Rani Thakur*1, Vipin Sardana1, M.M College of Pharmacy, M.M. University, Mullana,
Ambala-133001, India
Disintegrating Tablet of Salbutamol sulphate was selected as model drug In the present study, an attempt
had been made to prepare oral disintegrating tablets of the drug using various superdisintegrates
crospovidone, sodium starch glycolate, crosscarmellose sodium following bydirect compression
technique. Nine formulations having different superdisintegrants atdifferent concentration levels were
prepared to assess their efficiency and criticalconcentration level.

26. • Formulation and In-vitro Evaluation of Orally Disintegrating Tablets of Olanzapine-2-
Hydroxypropyl-β-Cyclodextrin Inclusion Complex :
Kulkarni Ajit Shankarrao*, Ghadge Dhairysheel Mahadeo and Kokate Pankaj Balavantrao, Depatment of Pharmaceutics,
Satara College of Pharmacy, Satara, M.S. India.
The aim of this study was to design orally disintegrating tablets of Olanzapine and to complex Olanzapine
with 2-hydroxypropyl-β- cyclodextrin with special emphasis on disintegration and dissolution studies.
• Formulation and In-vitro Evaluation of taste masked oral disintegrating tablets of
predisolone :
V. Ananda, *, R. Kandarapub, S. Gargc, Department of Pharmaceutics, Seth G. L. Bihani S. D. College of Technical
Education, Sri Ganganagar, Rajasthan, India b Research and Development, Dr. Reddy’s Laboratories Ltd. (Generics),
Bachupally, Hyderabad, India c School of Pharmacy, University of Aukland, New Zealand Received 20 June 2007;
Revised
18 September 2007; Accepted 13 October 2007
To prepare taste-masked orally disintegrating tablets (ODTs) of prednisolone (PDL) by incorporation of
microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients
experiencing difficulty in swallowing.
• Formulation and evaluation of Rizatriptan Benzoate Orally Disintegrating Tablets :
Mothilal. M*, Srikanth Kota, Sivagirish babu G, Gnanendra Kumar,
Manimaran. V and Damodharan. N Department of Pharmaceutics, SRM College of Pharmacy, SRM University,
Kattankulathur 603 203, Tamil Nadu, India.
Orally disintegrating benzoate were prepared by direct compression method to provide faster relief from
pain to migraine sufferers. About twelve formulations for tablets of Rizatriptan

27. • Formulation, Evaluation and Optimization of Orally Disintegrating Tablet of Piroxicam :
*Bhupendra G.Prajapati, Bhaskar Patel, S.K.Patel College of Pharmaceutical Education and Research,Ganpat University,
Kherva-382711, Mehsana, Gujarat State, INDIA
Objective of this study was to formulate directly compressible orally disintegrating tablets of piroxicam
with sufficient mechanical integrity, content uniformity, and acceptable palatability to assist patients of any
age group for easy administration. Effect of varying concentrations of different superdisintegrants such as
crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time was studied.
• Formulation And Evaluation Of Enalapril Maleate Orodispersible Tablet :
S.Jayaprakash, K.Kulathuran Pillai, S.Mohamed Halith*, Ganesh Doifode, Abirami, P.U.Mohamed Firthouse Department
of Pharmaceutics, K.M.College of Pharmacy, Madurai-625107, Tamilnadu, India.
In the present work Enalapril maleate tablet have been developed in an orodispersible tablets formulation
(ODT). Which was designed to facilitate tablet disintegration and drug dispersion. Orodispersible tablet of
Enalapril maleate which, when placed in the tongue disintegrates or dissolve rapidly in the saliva without
water.

28.  To formulate Oral disintegrating tablets for new generation drugs of Anti-
migraine for treating migraine.
Formulation Designing : 2n factorial design technique was used for formulation
designing. In this “2” is factor i.e. combination of two super disintegrants at a time and “n”
indicates level i.e. higher and lower concentration
 To Characterize interaction between the drugs & the excipients used.
 To Evaluate the prepared Oral disintegrating tablets.
 To Select an optimized formulation and compare it with the marketed products &
find the F2 value.

29. API’s :
Avitriptan, Clonidine Hydrochloride, Ergotamine Tartrate,
Naratriptan.
Excipients :
Sodium starch glycolate, Cross povidone, Crosscarmellose
sodium, Mannitol, Aerosil, Mg stearate, Aspartame, Flavours,
MCC

30. Avitriptan
IUPAC Name –
1-[3-[3-[4-(5-methoxypyrimidin-
4yl)piperazin-1-yl]propyl]-1H-indol-5-yl]-N-
methyl-methanesulfonamide .
Molecular formula - C22H30N6O3S
Molecular Weight - 458.577
Catergory - Indolylpiperazine compound with abortive antimigraine properties.
I
MOA - Avitriptan interacts with vascular 5-HT11-like receptors to constrict cerebral blood
vessels and reduce carotid artery blood flow by closing AV anastomoses (AV
shunts)that have been implicated in causing migraine pain .
The drug was rapidly absorbed after oral administration, with peak plasma concentrations
occurring at 0.5 hr postdose. Absolute bioavailability was 19.3% in rats and 17.2% in
humans.

31. Clonidine Hydrochloride
IUPAC Name –
N-(2,6-dichlorophenyl)-4,5-dihydro-1H-
imidazol-2-amine
Molecular formula - C9H10Cl3N3 Hcl
Molecular Weight - 266.5548
Catergory - Adrenergic alpha-2 Receptor Agonists.
MOA - Stimulates central alpha-adrenergic receptors to inhibit sympathetic
cardioaccelerator and vasoconstrictor centers.
T1/2 - 6-20 hours; 40-60% is excreted in urine unchanged, 20% is excreted in feces. Less
than 10% is excreted by p-hydroxyclonidine.
Bioavailability - 75-95%

32. Ergotamine Tartrate
IUPAC Name –
(6aR,9R)-N-((2R,5S,10aS,10bS)- 5-benzyl-10b-
hydroxy-2-methyl- 3,6-dioxooctahydro-2H-
oxazolo[3,2-a] pyrrolo[2,1-c]pyrazin-2-yl) -7-
methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]
quinoline-9-carboxamide
Molecular formula - C33H35N5O5)2, C4H6O6
Molecular mass - 1312.4 g/mol
Catergory - Vasoconstrictor Agents, Sympatholytics, Adrenergic, alpha-Agonists,
Analgesics, Non-Narcotic
.
MOA - Avitriptan interacts with vascular 5-HT11-like receptors to constrict cerebral blood
vessels and reduce carotid artery blood flow by closing AV anastomoses (AV
shunts)that have been implicated in causing migraine pain .
T1/2 - Is approximately 2 h; 90% of metabolites are excreted in the bile. Unmetabolized
ergotamine is erratically excreted in the saliva, and trace amounts are excreted in the
feces and urine.
Bioavailability - Intravenous: 100%, Intramuscular: 47%, Oral: <1% (Enhanced by co-
administration of caffeine

33. Naratriptan
IUPAC Name –
N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-
indol-5-yl]ethanesulfonamide
Molecular formula - C17H25N3O2
Molecular Weight - 335.465 [[gram g/mol
Catergory - 5HT (serotonin) agonist.
MOA - Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-
HT1 RECEPTORS. Included under this heading are agonists for one or more of
the specific 5-HT1 receptor subtypes.
Bioavailability - 74%
Metabolism - Hepatic
T1/2 - 5-8 hours
Excretion - Renal

34. • Minipress - II DL – Rimek
• Dissolution Tester(USP) - Electrolab
• Disintegration Tester(USP) - Electrolab
• Friabulator (USP) - Electrolab
• UV-Visible spectrometer - PG instruments LTD
• Digital pH meter – Systronics
• Digital balance
• Monsanto hardness tester

35. • Melting point test
• Solubility study
• Compatibility study
• Flow properties of API’s