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Review:
      On Mouth Dissolving Tablet

             Presented By
       S. B. THOKE [M. PHARM]
        [DEPT OF PHARMACEUTICS]
Content’s -

 Definition
 Significance
 Requirements of ODTs
 Formulation Methodologies
 Patented Technologies
 Superdisintegrants employed in ODT
 Evaluation
 References
                                       2
Definition


Fast Dissolving Tablets (FDTs) or “mouth dissolving
tablets” (MDTs) which disintegrates or dissolves
rapidly without water within few seconds in the
mouth.




                                                      3
According to European pharmacopoeia, these MDTs
should dissolve/disintegrate in less than three minutes.


US FDA defined ODTs as “A solid dosage form
containing medicinal substances or active ingredients
which disintegrates rapidly within a few seconds when
placed up on tongue”




                                                       4
Mouth dissolving tablets are also called as
 Orodispersible tablets (ODTs),
 Fast disintegrating tablets,
 Orally disintegrating tablets,
 Quick disintegrating tablets,
 Fast dissolving tablets,
 Rapid dissolving tablets,
 Porous tablets,
 Quick melt tablets &
 Rapid melt tablets.
                                              5
Significance
 It offer all advantages of solid dosage forms
  and liquid dosage forms along with special
  advantages, includes
 It provide good stability, accurate dosing, easy
  manufacturing, small packaging size & easy to
  handle.
 No need of water to swallow the dosage form.
 Easy to administer for paediatric, geriatric &
  institutionalized patients.
 More rapid drug absorption from the pre-
  gastric area which may produce Quick onset of
  action.                                            6
 Pre-gastric absorption of drug avoids hepatic
  metabolism, which reduces the dose and
  increase the bioavailability.
 The risk of chocking or suffocation during oral
  administration avoided.
 Good mouth feel property of MDDDS helps to
  change the basic view of medication as "bitter
  pill"
 Patient’s compliance for disabled bedridden
  patients and for travelling and busy people, who
  do not have ready access to water.



                                                 7
Requirements of ODTs
An ideal FDT should
I. Dissolve / disintegrate in the mouth in matter
     of seconds without water.
II. Have sufficient mechanical strength and good
     package design.
III. Not affected by drug properties.
IV. Effective taste masking technologies should be
     adopted for bitter taste drugs.
V. Leave minimal or no residue in mouth after
     oral administration.
VI. Exhibit low sensitivity to environment
     condition such as humidity and temperature.
                                                 8
Formulation Methodologies
 1.   Freeze drying or lyophilization
 2.   Molding
 3.   Cotton candy process
 4.   Spray drying
 5.   Mass extrusion
 6.   Nanonization
 7.   Three-dimensional Printing (3DP)
 8.   Compaction
 i)   Melt granulation
 j)   Phase transition process
 k)   Sublimation
                                         9
9. Conventional methods
b)Dry granulation
c)Wet granulation
d)Direct compression




                          10
1. Freeze drying or lyophilization
This process includes the removal of solvent from a
frozen suspension or solution of drug with
structure-forming additives.

Freeze-drying of drug along with additives imparts
glossy amorphous structure resulting in highly
porous and lightweight product.

MDTs formed by lyophilization have
  low mechanical strength,
  poor stability at higher temperature, and
  humidity
                                                  11
2. Molding
Molded tablets are prepared by using water-soluble
ingredients.

The powder blend is          moistened   with   a
hydroalcoholic solvent.

Molded into tablets under pressure lower than that
used in conventional tablet compression.
Solvent is then removed by air-drying.

Molded tablets are very less compact than
compressed tablets.
                                                 12
3. Cotton candy process

This process involves formation of matrix of
polysaccharides or saccharides by simultaneous
action of flash melting and spinning.

Formed matrix is partially re-crystallized to have
improved flow properties and compressibility.

This candy floss matrix is then milled.

Blended with active ingredients and excipients and
subsequently compressed to FDTs.
                                                 13
4. Spray drying

In this method hydrolyzed and nonhydrolyzed
gelatin were used as supporting matrix.

Mannitol as bulking agent

Sodium starch glycolate or crosscarmellose sodium
as superdisintegrant.

Acidic substances (citric acid) or alkali substance
(sodium       bicarbonate)      further    increase
disintegration and dissolution.

                                                  14
This technology produces highly porous and fine
powders as processing solvent is evaporated during
process.

Disintegration time < 20 sec




                                                 15
5. Mass extrusion

Involves softening the active blend using the
solvent mixture of water-soluble polyethylene
glycol and methanol.

Subsequent expulsion of softened mass through the
extruder or syringe.

To get a cylinder of the product into even
segments using heated blade to form tablets.



                                                16
6. Nanonization
Nanomelt technology involves reduction in the
particle size of drug by proprietary wet-milling
technique.
Nanocrystals of the drug are stabilized against
agglomeration by surface adsorption on selected
stabilizers, which are then incorporated into MDTs.
Advantages
For poor water soluble drugs.
Fast            disintegration/dissolution       of
nanoparticles . .. leads to increased absorption and
bioavailability.
Reduction in dose.
                                                   17
7. Three-dimensional Printing (3DP)
It is a rapid prototyping (RP) technology.
Prototyping involves constructing specific layers
that uses powder processing and liquid binding
materials.
Loose powders in it was fabricated using 3DP
process.
Based on computer-aided design models
TAG tablets seemed due to the rapid water
penetration into the tablet resulting from the large
pore size
                                                   18
8. Compaction
a) Melt granulation


Powders are efficiently agglomerated by a melt able
binder.
Advantages:- No water or organic solvents is
needed.
For this, purpose high shear mixers are utilized.
Product temperature is raised above the melting
point of binder by a heating jacket or by the heat of
friction generated by impeller blades.
                                                    19
It involves the use of a hydrophilic waxy binder
(Superpolystate©, PEG-6-stearate).

Superpolystate© having melting point 33–37°C and
a HLB value 9.

So it will not only act as a binder but will also help
the disintegration.




                                                     20
b) Phase transition process

In this compress powder containing erythritol
(melting point: 122 °C) and xylitol (melting point:
93 - 95 °C), and then heating at about 93 °C for 15
min.
After heating, the median pore size and tablet
hardness was increased.

Heating process enhances the bonding among
particles leads to sufficient hardness of tablets.



                                                  21
c) Sublimation
When inert volatile solid ingredients like
ammonium bicarbonate, ammonium carbonate,
benzoic acid, camphor, hexamethylene tetramine,
naphthalene, phthalicanhydride, urea and urethane
were added to other tablet excipients.
Blend was compressed in to a table & finally
subjected to sublimation resulting in highly porous
structures.
Tablets produce by this method exhibit
  good mechanical strengthhigh,
  porosity (approximately 30%),
  dissolved within 15 seconds in saliva.
                                                  22
Figure:- Steps Involved in sublimation   23
9. Conventional methods
a) Direct compression

Easiest way to manufacture tablets.
Conventional equipment, commonly available
excipients and a limited number of processing steps
are involved in direct compression.
Also high doses can be accommodated and final
weight of tablet can easily exceed that of other
production methods.

Tablet disintegration time can be optimized by
concentrating the disintegrants.
                                                  24
Below critical concentration, tablet disintegration
time is inversely proportional to disintegrants
concentration.
Above      the    critical  concentration   level,
disintegration time remains approximately constant
or even increases.
The major drawback of effervescent excipients is
their hygroscopicity (i.e., the ability to absorb
atmospheric moisture).
Another approach is the use of sugar‐based
excipients (e.g., dextrose, fructose, isomalt,
maltitok, maltose, mannitol, sorbitol, starch
hydrolyse, polydextrose, and xylitol).       25
Which are having high aqueous solubility and
sweetness.

It impart taste masking and a pleasing mouthfeel.

Microcrystalline       cellulose, cross      linked
carboxymethyl cellulose sodium, cross linked
polyvinyl pyrrolidone and partially substituted
hydroxypropyl cellulose, though water insoluble,
absorb water and swell due to capillary action and
act as effective disintegrants.




                                                    26
b) Wet granulation

Acid component of the effervescent couple
presented in the tablet with lower than 5%, quick
disintegration times could be achieved.
In the patent, the formulation includes polyalcohols
(e.g., mannitol, xylitol, sorbitol, maltitol, erythritol,
and lactitol).

1–30% of an edible acid & an active ingredient as
the dry mixture wet granulated with an aqueous
solution of a water-soluble or water-dispersible
polymer (e.g., poly(ethylene glycols), carrageenan,
and ethylcellulose).
                                                        27
which consisted of 1–10% of the final weight of
the granule in a fluid bed.

Granules with high porosity and low apparent
density disintegration times ranging from 3 to 30
seconds in the saliva were obtained.




                                                28
c) Dry granulation

Low-density alkali earth metal salts or water-
soluble carbohydrates were precompacted, and the
resulting granules were compressed into tablets.

Powdered material with a density of 0.2–0.55
g/mL was precompacted to increase the density to
0.4–0.75 g/mL by applying a force ranging from 1
to 9 kN/cm.

The resulting granules were compressed into
tablets.

                                                   29
Patented Technologies
1. OraSolv technology
OraSolv technology (Cima Labs) produces tablets
by low compression pressure
It uses an effervescent disintegration pair that
releases gas upon contact with water.
Widely used effervescent disintegration pairs
       Acid sources              Carbonate sources
Citric acid, Tartaric acid,   Sodium bicarbonate,
Malic acid, Fumaric           Sodium carbonate,
acid, Adipic acid, and        Potassium bicarbonate,
Succinic acids.               and Potassium carbonate.
                                                         30
The carbon dioxide evolved from the reaction may
provide some “fizzing” sensation, which is a
positive organoleptic sensation.
20–25% of total weight of tablet effervescent agent
is used.
OraSolv tablets - soft and fragile nature.
PakSolv - Special packaging system
 “Dome-shaped” blister package
 Prevents the vertical movement of the tablet
within the depressions.
 Protect the tablets from breaking during transport
and storage also offers light, moisture, and child
resistance.
                                                      31
2. DuraSolv Technology
Developed by Ciba, second-generation technology.
To Produce stronger tablets for packaging in
blisters or bottles.
Tablets have low friability, about 2% or less when
tested according to the USP.
Hardness of the tablets - at least about 15–20 N.
Disintegration time is less than 60 seconds.
By Direct compression method tablets produce.
conventional tableting methodologies & conven-
tional package equipment are used.
                                                     32
Key ingredients -
 Non-direct compression filler and lubricant.
Non-direct compression filler -
 particle size 20-65 μm.
   e.g. dextrose, mannitol, sorbitol, lactose, &
sucrose.
  advantage - quick dissolution and avoid gritty or
sandy texture.
 60–95% amount of the total tablet weight is used.

Direct compressible fillers –
 at least 85% of the particles are over 100 μm size.
 Have some of the gritty or sandy texture.

                                                       33
Higher amounts (1–2.5%) of hydrophobic
lubricants, such as magnesium stearate, can be
added.
lubricant blending times can also be increased to
10–25 minutes or longer.

0.2–1% lubricant in conventional tablets.

Relatively modest compressive force is needed to
compress the formulation.




                                                    34
3. WOWTAB Technology
Patented by "Yamanouchi Pharmaceutical Co. "
WOW means "Without Water ".

In this process, API is mixed with a low
mouldability saccharide and granulated with a high
mouldability saccharide and compressed into
tablet.

There is no single saccharide that can make tablets
having both high strength and fast disintegration
properties.

                                                      35
Low moldability saccharides
e.g. lactose, mannitol, glucose, sucrose, and
xylitol.

Tablets with hardness 0-2 kg, when 150 mg of
such a saccharide is compressed under pressure of
10–50 kg/cm2 using a die 8 mm in diameter.

High-moldability saccharides
e.g. maltose, oligosaccharides, maltitol, & sorbitol.

Produce tablets with hardness above 2 kg when
prepared under identical conditions.
The typical high- moldability saccharides are
                                                        36
4. Flashtab Technology
Prographarm laboratories     have   patented   the
Flashtab technology.

Drug micro granules may be prepared by using the
conventional techniques like coacervation, micro
encapsulation, and extrusion spheronisation.
Excipients mixtureis prepared by either dry or wet
granulation methods.

Excipients used - two groups of components:
1] Disintegrating agents- carboxymethylcellulose
or insoluble reticulated polyvinylpyrrolidone; and
                                                     37
2] Swelling agents- carboxymethylcellulose,
starch, modified starch, carboxymethylated
starch, microcrystalline cellulose, and possibly
directly compressible sugars.




                                                   38
5. AdvaTab Technology
Patented by Kyowa Hakko Kogyo
Lubrication is dispensed onto each tablet by using
a spray.
10–30 times less hydrophobic lubricant employed
& 30–0% stronger than conventional tablets.
Handle high drug loading and coated drug
particles.

Traditional tablets produced using an internal
lubrication system, which disperses lubricant on
the inside and the surface of the tablets, decrease
tablet mechanical strength.
                                                      39
6. Dispersible Tablet Technology
Lek in Yugoslavia was issued patents for
dispersible tablets of dihydroergotoxine and
cimetidine

Dihydroergotoxine is poorly water soluble in free
base form.

Improved dissolution rate of dihydroergotoxine
methanesulphonate was observed with dispersible
tablets containing 0.8– 10%, preferably about 4%
by weight, of an organic acids.

                                                40
Cimetidine formulated with one of disintegrating
agent. It provides rapid swelling and/or good
wetting capability to the tablets and thereby a quick
disintegration.
Disintegrating agents
e.g. starch or modified starches, microcrystalline
cellulose, alginic acid, cross-linked sodium
carboxymethyl cellulose, and cyclodextrin
polymers.

Combination of two or more disintegrating agents
produced better disintegration results.

                                                     41
7. Pharmaburst Technology
Process involves a dry blend of a drug, flavor, and
lubricant that are compressed into tablets on a
standard tablet press with stock tooling.
uses off- the-shelf coprocessed excipients,
depending on the type of active and loading (up to
700mg), dissolves within 30–40 seconds.

Manufacture process can be carried out under
normal temperature and humanity conditions.

The tablets can be packaged in blister packs or
bottle.
                                                      42
8. OraQuick technology
It utilizes a patented taste masking technology.
KV Pharmaceutical claims its microsphere
technology, known as MicroMask.
Taste masking process does not utilize solvents of
any kind, it leads to faster and more efficient
production.
Lower heat of production than alternative fast‐
dissolving/disintegrating technologies makes
OraQuick appropriate for heat‐sensitive drugs.
Matrix that surrounds and protects the drug
powder in microencapsulated particles is more
pliable.                                      43
Tablets can be compressed to achieve significant
mechanical strength without disrupting taste
masking.

KV Pharmaceutical has products in development
such as analgesics, scheduled drugs, cough and
cold, psychotropics, and anti‐infectives




                                               44
9. Quick –Dis technology
Lavipharm Laboratories Inc. (Lavipharm) invented
this ideal intraoral FDDS.
Thin, flexible, and quick‐dissolving film.
Quick‐Dis™ provided in various packaging
configurations, unit‐dose pouches to multiple‐dose
blister packages.

Film with a thickness of 2 mm have disintegration
time 5 to 10 seconds & dissolving time, is around
30 seconds.
Typical release profile of API is 50% released
within 30 seconds and 95% within 1 minute.     45
10. Zydis technology
Zydis is a unique freeze dried oral solid dosage
form.
Dissolves in less than 3 seconds.
Drug is physically trapped in a water soluble
matrix, and then freeze dried.

Thirteen products are currently available based on
zydis technology.

 In worldwide market, zydis formulations
 available for oxazepam, lorazepam, loperamide,
 and enalapril.
                                                     46
Matrix contain excipients like
1] Polymers (e.g., gelatine, alginates, and dextrin)
to provide strength and rigidity to tablets;
2] Polysaccharides (e.g.,mannitol and sorbitol)
to impart crystallinity and hardness to the matrix
and to improve palatability;
3] Collapse protectants (e.g, glycin)
to prevent the product from shrinking in its
packaging during manufacturing or storage;
4] Flocculating agents (e.g, xanthan gum and
acacia)
to provide uniform dispersion of drug particles;
5] Preservatives(e.g., parabens)
to prevent microbial growth;
                                                       47
6] Permeation enhancers (e.g., sodium lauryl
sulphate)
to improve transmucosal permeability;
7] pH adjusters (e.g, citric acid)
to optimize chemical stability;
8] Flavours and sweeteners
to improve patient compliance and
9] water to ensure formation of porous units.

In US, zydis products available-
Claritin Reditab, Dimetapp Quick Dissolve,
Feldene Melt, Maxalt-MLT, Pepcid RPD, Zofran
FDT, and Zyprexa Zydis.
                                                48
11. Frosta technology
Patented by Akina.
It utilizes core concept of formulating plastic
granules and compressing at low pressure to
produce strong tablets with high porosity.
Process involves mixing the porous plastic
material with water penetration enhancer and
granulated with binder.
Used for - aspirin, loratidine, caffeine, and folic
acid, vitamins and dietary supplements.



                                                      49
Superdisintegrants employed in ODT
    Super       Commercially        Mechanism of            Special
disintegrants available grades          action            comment
Crosslinked   Crosscarmellose®   Swells 4-8 folds in  Swells in two
Cellulose     Ac-Di-Sol®,        < 10 seconds.        dimensions.
              Nymce ZSX®         Swelling and         Direct
              Primellose®,       wicking both.        compression or
              Solutab®,                               Granulation
              Vivasol®, L-HPC                         Starch free.
Crosslinked   Crosspovidon M®    Swells very little   Water insoluble
PVP           Kollidon®          and returns to       and
              Polyplasdone®      original size after  spongy in nature
                                 compression but act so get porous
                                 by capillary action. tablet.



                                                                     50
Crosslinked        Explotab®      Swells 7-12 folds in   Swells in three
starch             Primogel®      < 30 seconds.          dimensions
                                                         and high level
                                                         serve as sustain
                                                         release matrix.
Crosslinked        Alginic acid   Rapid swelling in      Promote
alginic            NF             aqueous medium or      disintegration
Acid                              wicking action.        in both dry or wet
                                                         granulation.
Soy             Emcosoy®                                 Does not contain
Polysaccharides                                          any starch or
                                                         Sugar. Used in
                                                         Nutritional
                                                         products.
Calcium silicate                  Wicking action         Highly porous,
                                                         Light weight.
                                                                            51
Marketed product of MDTs
Brand name        Active ingredient   Application     company
Claritin®         Loratadine          Antihistamine   Scherig
RediTabs®                                             corporation
Feldene Melt®     Piroxicam           NSAIDs          Pfizer
Maxalt® -MLT®     Rizatritpan         Migrane         Merck
                  benzoate
Pepeid® ODT       Femotidene          Anti-ulcer      Merck
Zyperxa®          Olazepine           Psychotropic    Eli Lilly
Zofran® ODT       Olandansetron       Antiemetic      Galaxo Smith
                                                      kline
Resperdal® M-     Resperidone         Schizophrenia   Janssen
Tab TM
Klonopin® wafer   Clonazepam          Sedation        Roche
Imodium Istant    Loperamide HCL      Antidiarrheal   Jannsen
Melts
Nasea OD          Ramosetoron HCl     Anti-emetic     Yamanouchi
Tempra            Acetaminophen       Analgesic       Bristol-M
Quicksolv®                                            ters squibb
                                                                    52
Preformulation Studies
1. Bulk Density
Formula

Where :
ρb - Bulk density, M- Weight of powder, and
V- Volume of powder.
2. Tapped Density
Formula
                  ρt = M / Vt
Where :
ρt - Tapped density, M- Weight of powder, and
Vt- Minimum volume occupied after tapping.
                                                53
3. Compressibility Index

Simplest way for measurement of flow of powder.
Formula
           % C.I. = ρt – ρb/ρt x100

4. Hausner ratio
 Hausner ratio is an indirect index of ease of
 powder flow.
 Lower the value of Housner ratio better is the flow
 property.
 Formula
            Hausner ratio = ρt/ ρb
                                                   54
Flow property   % C.I.   Hosner ratio

 Excellent       ≤10       1.00-1.11
   Good         11-15      1.12-1.18
    Fair        16-20      1.19-1.25
  Passable      21-25      1.26-1.34
   Poor         26-31      1.35-1.45
 Very poor      32-37      1.46-1.59
 Very, very      >38          >1.6
    poor

                                        55
5. Porosity
Formula
              ε = ( 1 - ρapp / ρtrue) X 100
Where,
ε- Porosity, ρapp- Apparent density, and
ρtrue- True density.
6.Voide Volume
 Formula
              V = Vb - Vp
 Where,
 V- Voide volume, Vb- Bulk volume, and
 Vp- Tapped volume.

                                              56
7. Angle of repose
Formula
             ϴ = Tan-1 ( h / r )
Where,
ϴ- Angle of repose, h- Hight of the heap, and
r- Radius of the heap.
    Flow property          Angle of repose (degrees)
        Excellent                     25-30
          Good                        31-35
  Fair- aid not needed                36-40
 Passable- must agitate,              41-45
         vibrate
          Poor                        46-55
       Very poor                      56-65
    Very, very poor                    >66             57
Evaluation of Mouth dissolving
1. Thickness
Measured using Vernier calipers.
2. Hardness
Force required to break a tablet by compression in
the radial direction.
Pfizer hardness testers   Monsanto hardness tester.




                                                      58
3. Uniformity of weight

20 tablets randomly take from lot and weighted
individually to check for weight variation.

     Weight variation specification as per IP
   Average weight of tablet         % Deviation
         80 mg or less                 ±10
  More than 80 mg but less than        ±7.5
            250 mg
        250 mg or more                   ±5



                                                  59
4. In-vitro dispersion time test
Drop a tablet in a beaker containing 50ml of
sorrenson’s buffer pH 6.8 & time required for
complete dispersion was determined.




                                            60
5. Friability test
Determined using Roche friability.
Subjected to 100 revolutions (25rpm/minute).
Formula
             f = (1- W0 / W) × 100
Where,
f- Friability, W0- Weight of the tablets before, and
W- Weight of the tablet after the test.

6. In vivo Disintegration time

Time required for complete disintegration of
tablets in oral cavity determined by administering
tablets to 10 healthy volunteers.                 61
7. Wetting time
Tablet is placed on a piece of tissue paper folded
twice and kept in a Petri dish (ID = 6.5 cm)
containing 6 ml of water, and the time for complete
wetting is measured.

8. Water absorption ratio
 This test performed as like wetting time
 Formula
            R = 10 ( Wa /Wb)
 Where,
 R- Water absorption ratio, Wb- Weight of tablet
 before water absorption, & Wa- weight of tablet
 after water absorption.                           62
9. Dissolution test

Dissolution study performed using USP       II
apparatus (paddal speed 50rpm).
USP monographs dissolutions conditions should
be followed in addition 0.1N HCl, pH 4.5 & 6.8
buffers should be evaluated.
10. Stability study
As per ICH Q1A guidelines for accelerated
studies.
Tablets stored at 40±1ºC/75% ± 5% RH for 4
weeks.
                                                 63
Afterword withdraw & analyse for physical
characterization (visual defects, hardness,
friability, disintegration, dissolution etc.) drug
content.




                                                     64
Promising Drugs to be incorporated In FDT
Analgesics and Anti-inflammatory Agents
Anti-Arrhythmic Agents
Anti-bacterial Agents
Anti-coagulants
Anti-Epileptics
Anti-Fungal Agents
Anti-Gout Agents
Anti-Hypertensive Agents
Anti-Malarials
Anti-Neoplastic Agents And Immunosuppressants
Anti Protozoal Agents
Anti-Muscarinic Agents
Anti-Parkinson Agents
                                                65
Gastro-Intestinal Agents
Histamine H,-Receptor Antagonists
Stimulants
Lipid Regulating Agents
Local Anaesthetics
Neuro -Muscular Agents
Nitrates And Other Anti-Anginal Agents
Nutritional Agents
Opioid Analgesics
Oral Vaccines
Proteins, Peptides And Recombinant Drugs
Sex Hormones
Anti-Thyroid Agents
Anxiolytic, Sedatives, Hypnotics And Neuroleptics
Tj-Blockers
                                                    66
Cardiac Inotropic Agents
Corticosteroids
Enzymes
Diuretics




                           67
References
 Prashant B Pawar, “MOUTH DISSOLVING TABLET: A REVIEW”,
International Journal of Herbal Drug Research, Vol I, Issue II;2011, Page
no.- 22-29.
Debjit Bhowmik, “Fast dissolving tablet: A review on revolution of
novel drug delivery system and new market opportunities” Scholars
Research Library, Der Pharmacia Lettre, 1 (2); 2009, Page no.- 262-276.
 Alok Kumar Gupta, “Fast Dissolving Tablet- A Review”, The Pharma
Innovation, Vol. 1(1); 2012, ISSN 2277-7695, Page no.- 1- 7.
 V. Dinesh kumar, “A comprehensive review on fast dissolving tablet
technology”, Journal of Applied Pharmaceutical Science, 01 (05); 2011,
ISSN: 2231-3354, Page no.- 50-58.
 A. Gupta, “Recent Trends of Fast Dissolving Tablet - An Overview of
Formulation Technology”, International Journal of Pharmaceutical &
Biological Archives, 1(1); 2010, Page no.- 1-10.

                                                                        68
 Velmurugan S., “Oral Disintegrating Tablets: An Overview”,
International Journal of Chemical and Pharmaceutical Sciences, Vol.1 (2);
Dec. 2010, Page no.- 1-12.
 P. Ashish, “A Review- Formulation of Mouth Dissolving tablet”,
International Journal of Pharmaceutical and Clinical Science, 1 (1); 2011,
Page no.- 1-8.
 Bhupendra G Prajapati, “A Review on Recent patents on Fast
Dissolving Drug Delivery System”, International Journal of Pharm Tech
Research CODEN( USA): IJPRIF ISSN : 0974-4304, Vol.1, No.3; July-
Sept 2009, Page no.- 790-798.
 Mukesh P. Ratnaparkhi, “Review On: Fast Dissolving Tablet”, Journal
of Pharmacy Research, Vol.2, Issue 1; January 2009, Page no.- 5-12.
 Tejvir Kaur, “Mouth Dissolving Tablets: A Novel Approach To Drug
Delivery”, International Journal of Current Pharmaceutical Research,
ISSN- 0975-7066, Vol 3, Issue 1; 2011, Page no.- 1-7.
 Jaysukh J Hirani, “Orally Disintegrating Tablets: A Review”, Tropical
Journal of Pharmaceutical Research, 8 (2); April 2009, Page no.- 161-172

                                                                        69
Thank u…!




            70

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Review On Mouth Dissolving Tablet

  • 1. Review: On Mouth Dissolving Tablet Presented By S. B. THOKE [M. PHARM] [DEPT OF PHARMACEUTICS]
  • 2. Content’s -  Definition  Significance  Requirements of ODTs  Formulation Methodologies  Patented Technologies  Superdisintegrants employed in ODT  Evaluation  References 2
  • 3. Definition Fast Dissolving Tablets (FDTs) or “mouth dissolving tablets” (MDTs) which disintegrates or dissolves rapidly without water within few seconds in the mouth. 3
  • 4. According to European pharmacopoeia, these MDTs should dissolve/disintegrate in less than three minutes. US FDA defined ODTs as “A solid dosage form containing medicinal substances or active ingredients which disintegrates rapidly within a few seconds when placed up on tongue” 4
  • 5. Mouth dissolving tablets are also called as  Orodispersible tablets (ODTs),  Fast disintegrating tablets,  Orally disintegrating tablets,  Quick disintegrating tablets,  Fast dissolving tablets,  Rapid dissolving tablets,  Porous tablets,  Quick melt tablets &  Rapid melt tablets. 5
  • 6. Significance  It offer all advantages of solid dosage forms and liquid dosage forms along with special advantages, includes  It provide good stability, accurate dosing, easy manufacturing, small packaging size & easy to handle.  No need of water to swallow the dosage form.  Easy to administer for paediatric, geriatric & institutionalized patients.  More rapid drug absorption from the pre- gastric area which may produce Quick onset of action. 6
  • 7.  Pre-gastric absorption of drug avoids hepatic metabolism, which reduces the dose and increase the bioavailability.  The risk of chocking or suffocation during oral administration avoided.  Good mouth feel property of MDDDS helps to change the basic view of medication as "bitter pill"  Patient’s compliance for disabled bedridden patients and for travelling and busy people, who do not have ready access to water. 7
  • 8. Requirements of ODTs An ideal FDT should I. Dissolve / disintegrate in the mouth in matter of seconds without water. II. Have sufficient mechanical strength and good package design. III. Not affected by drug properties. IV. Effective taste masking technologies should be adopted for bitter taste drugs. V. Leave minimal or no residue in mouth after oral administration. VI. Exhibit low sensitivity to environment condition such as humidity and temperature. 8
  • 9. Formulation Methodologies 1. Freeze drying or lyophilization 2. Molding 3. Cotton candy process 4. Spray drying 5. Mass extrusion 6. Nanonization 7. Three-dimensional Printing (3DP) 8. Compaction i) Melt granulation j) Phase transition process k) Sublimation 9
  • 10. 9. Conventional methods b)Dry granulation c)Wet granulation d)Direct compression 10
  • 11. 1. Freeze drying or lyophilization This process includes the removal of solvent from a frozen suspension or solution of drug with structure-forming additives. Freeze-drying of drug along with additives imparts glossy amorphous structure resulting in highly porous and lightweight product. MDTs formed by lyophilization have low mechanical strength, poor stability at higher temperature, and humidity 11
  • 12. 2. Molding Molded tablets are prepared by using water-soluble ingredients. The powder blend is moistened with a hydroalcoholic solvent. Molded into tablets under pressure lower than that used in conventional tablet compression. Solvent is then removed by air-drying. Molded tablets are very less compact than compressed tablets. 12
  • 13. 3. Cotton candy process This process involves formation of matrix of polysaccharides or saccharides by simultaneous action of flash melting and spinning. Formed matrix is partially re-crystallized to have improved flow properties and compressibility. This candy floss matrix is then milled. Blended with active ingredients and excipients and subsequently compressed to FDTs. 13
  • 14. 4. Spray drying In this method hydrolyzed and nonhydrolyzed gelatin were used as supporting matrix. Mannitol as bulking agent Sodium starch glycolate or crosscarmellose sodium as superdisintegrant. Acidic substances (citric acid) or alkali substance (sodium bicarbonate) further increase disintegration and dissolution. 14
  • 15. This technology produces highly porous and fine powders as processing solvent is evaporated during process. Disintegration time < 20 sec 15
  • 16. 5. Mass extrusion Involves softening the active blend using the solvent mixture of water-soluble polyethylene glycol and methanol. Subsequent expulsion of softened mass through the extruder or syringe. To get a cylinder of the product into even segments using heated blade to form tablets. 16
  • 17. 6. Nanonization Nanomelt technology involves reduction in the particle size of drug by proprietary wet-milling technique. Nanocrystals of the drug are stabilized against agglomeration by surface adsorption on selected stabilizers, which are then incorporated into MDTs. Advantages For poor water soluble drugs. Fast disintegration/dissolution of nanoparticles . .. leads to increased absorption and bioavailability. Reduction in dose. 17
  • 18. 7. Three-dimensional Printing (3DP) It is a rapid prototyping (RP) technology. Prototyping involves constructing specific layers that uses powder processing and liquid binding materials. Loose powders in it was fabricated using 3DP process. Based on computer-aided design models TAG tablets seemed due to the rapid water penetration into the tablet resulting from the large pore size 18
  • 19. 8. Compaction a) Melt granulation Powders are efficiently agglomerated by a melt able binder. Advantages:- No water or organic solvents is needed. For this, purpose high shear mixers are utilized. Product temperature is raised above the melting point of binder by a heating jacket or by the heat of friction generated by impeller blades. 19
  • 20. It involves the use of a hydrophilic waxy binder (Superpolystate©, PEG-6-stearate). Superpolystate© having melting point 33–37°C and a HLB value 9. So it will not only act as a binder but will also help the disintegration. 20
  • 21. b) Phase transition process In this compress powder containing erythritol (melting point: 122 °C) and xylitol (melting point: 93 - 95 °C), and then heating at about 93 °C for 15 min. After heating, the median pore size and tablet hardness was increased. Heating process enhances the bonding among particles leads to sufficient hardness of tablets. 21
  • 22. c) Sublimation When inert volatile solid ingredients like ammonium bicarbonate, ammonium carbonate, benzoic acid, camphor, hexamethylene tetramine, naphthalene, phthalicanhydride, urea and urethane were added to other tablet excipients. Blend was compressed in to a table & finally subjected to sublimation resulting in highly porous structures. Tablets produce by this method exhibit good mechanical strengthhigh, porosity (approximately 30%), dissolved within 15 seconds in saliva. 22
  • 23. Figure:- Steps Involved in sublimation 23
  • 24. 9. Conventional methods a) Direct compression Easiest way to manufacture tablets. Conventional equipment, commonly available excipients and a limited number of processing steps are involved in direct compression. Also high doses can be accommodated and final weight of tablet can easily exceed that of other production methods. Tablet disintegration time can be optimized by concentrating the disintegrants. 24
  • 25. Below critical concentration, tablet disintegration time is inversely proportional to disintegrants concentration. Above the critical concentration level, disintegration time remains approximately constant or even increases. The major drawback of effervescent excipients is their hygroscopicity (i.e., the ability to absorb atmospheric moisture). Another approach is the use of sugar‐based excipients (e.g., dextrose, fructose, isomalt, maltitok, maltose, mannitol, sorbitol, starch hydrolyse, polydextrose, and xylitol). 25
  • 26. Which are having high aqueous solubility and sweetness. It impart taste masking and a pleasing mouthfeel. Microcrystalline cellulose, cross linked carboxymethyl cellulose sodium, cross linked polyvinyl pyrrolidone and partially substituted hydroxypropyl cellulose, though water insoluble, absorb water and swell due to capillary action and act as effective disintegrants. 26
  • 27. b) Wet granulation Acid component of the effervescent couple presented in the tablet with lower than 5%, quick disintegration times could be achieved. In the patent, the formulation includes polyalcohols (e.g., mannitol, xylitol, sorbitol, maltitol, erythritol, and lactitol). 1–30% of an edible acid & an active ingredient as the dry mixture wet granulated with an aqueous solution of a water-soluble or water-dispersible polymer (e.g., poly(ethylene glycols), carrageenan, and ethylcellulose). 27
  • 28. which consisted of 1–10% of the final weight of the granule in a fluid bed. Granules with high porosity and low apparent density disintegration times ranging from 3 to 30 seconds in the saliva were obtained. 28
  • 29. c) Dry granulation Low-density alkali earth metal salts or water- soluble carbohydrates were precompacted, and the resulting granules were compressed into tablets. Powdered material with a density of 0.2–0.55 g/mL was precompacted to increase the density to 0.4–0.75 g/mL by applying a force ranging from 1 to 9 kN/cm. The resulting granules were compressed into tablets. 29
  • 30. Patented Technologies 1. OraSolv technology OraSolv technology (Cima Labs) produces tablets by low compression pressure It uses an effervescent disintegration pair that releases gas upon contact with water. Widely used effervescent disintegration pairs Acid sources Carbonate sources Citric acid, Tartaric acid, Sodium bicarbonate, Malic acid, Fumaric Sodium carbonate, acid, Adipic acid, and Potassium bicarbonate, Succinic acids. and Potassium carbonate. 30
  • 31. The carbon dioxide evolved from the reaction may provide some “fizzing” sensation, which is a positive organoleptic sensation. 20–25% of total weight of tablet effervescent agent is used. OraSolv tablets - soft and fragile nature. PakSolv - Special packaging system  “Dome-shaped” blister package  Prevents the vertical movement of the tablet within the depressions.  Protect the tablets from breaking during transport and storage also offers light, moisture, and child resistance. 31
  • 32. 2. DuraSolv Technology Developed by Ciba, second-generation technology. To Produce stronger tablets for packaging in blisters or bottles. Tablets have low friability, about 2% or less when tested according to the USP. Hardness of the tablets - at least about 15–20 N. Disintegration time is less than 60 seconds. By Direct compression method tablets produce. conventional tableting methodologies & conven- tional package equipment are used. 32
  • 33. Key ingredients - Non-direct compression filler and lubricant. Non-direct compression filler - particle size 20-65 μm. e.g. dextrose, mannitol, sorbitol, lactose, & sucrose. advantage - quick dissolution and avoid gritty or sandy texture. 60–95% amount of the total tablet weight is used. Direct compressible fillers – at least 85% of the particles are over 100 μm size. Have some of the gritty or sandy texture. 33
  • 34. Higher amounts (1–2.5%) of hydrophobic lubricants, such as magnesium stearate, can be added. lubricant blending times can also be increased to 10–25 minutes or longer. 0.2–1% lubricant in conventional tablets. Relatively modest compressive force is needed to compress the formulation. 34
  • 35. 3. WOWTAB Technology Patented by "Yamanouchi Pharmaceutical Co. " WOW means "Without Water ". In this process, API is mixed with a low mouldability saccharide and granulated with a high mouldability saccharide and compressed into tablet. There is no single saccharide that can make tablets having both high strength and fast disintegration properties. 35
  • 36. Low moldability saccharides e.g. lactose, mannitol, glucose, sucrose, and xylitol. Tablets with hardness 0-2 kg, when 150 mg of such a saccharide is compressed under pressure of 10–50 kg/cm2 using a die 8 mm in diameter. High-moldability saccharides e.g. maltose, oligosaccharides, maltitol, & sorbitol. Produce tablets with hardness above 2 kg when prepared under identical conditions. The typical high- moldability saccharides are 36
  • 37. 4. Flashtab Technology Prographarm laboratories have patented the Flashtab technology. Drug micro granules may be prepared by using the conventional techniques like coacervation, micro encapsulation, and extrusion spheronisation. Excipients mixtureis prepared by either dry or wet granulation methods. Excipients used - two groups of components: 1] Disintegrating agents- carboxymethylcellulose or insoluble reticulated polyvinylpyrrolidone; and 37
  • 38. 2] Swelling agents- carboxymethylcellulose, starch, modified starch, carboxymethylated starch, microcrystalline cellulose, and possibly directly compressible sugars. 38
  • 39. 5. AdvaTab Technology Patented by Kyowa Hakko Kogyo Lubrication is dispensed onto each tablet by using a spray. 10–30 times less hydrophobic lubricant employed & 30–0% stronger than conventional tablets. Handle high drug loading and coated drug particles. Traditional tablets produced using an internal lubrication system, which disperses lubricant on the inside and the surface of the tablets, decrease tablet mechanical strength. 39
  • 40. 6. Dispersible Tablet Technology Lek in Yugoslavia was issued patents for dispersible tablets of dihydroergotoxine and cimetidine Dihydroergotoxine is poorly water soluble in free base form. Improved dissolution rate of dihydroergotoxine methanesulphonate was observed with dispersible tablets containing 0.8– 10%, preferably about 4% by weight, of an organic acids. 40
  • 41. Cimetidine formulated with one of disintegrating agent. It provides rapid swelling and/or good wetting capability to the tablets and thereby a quick disintegration. Disintegrating agents e.g. starch or modified starches, microcrystalline cellulose, alginic acid, cross-linked sodium carboxymethyl cellulose, and cyclodextrin polymers. Combination of two or more disintegrating agents produced better disintegration results. 41
  • 42. 7. Pharmaburst Technology Process involves a dry blend of a drug, flavor, and lubricant that are compressed into tablets on a standard tablet press with stock tooling. uses off- the-shelf coprocessed excipients, depending on the type of active and loading (up to 700mg), dissolves within 30–40 seconds. Manufacture process can be carried out under normal temperature and humanity conditions. The tablets can be packaged in blister packs or bottle. 42
  • 43. 8. OraQuick technology It utilizes a patented taste masking technology. KV Pharmaceutical claims its microsphere technology, known as MicroMask. Taste masking process does not utilize solvents of any kind, it leads to faster and more efficient production. Lower heat of production than alternative fast‐ dissolving/disintegrating technologies makes OraQuick appropriate for heat‐sensitive drugs. Matrix that surrounds and protects the drug powder in microencapsulated particles is more pliable. 43
  • 44. Tablets can be compressed to achieve significant mechanical strength without disrupting taste masking. KV Pharmaceutical has products in development such as analgesics, scheduled drugs, cough and cold, psychotropics, and anti‐infectives 44
  • 45. 9. Quick –Dis technology Lavipharm Laboratories Inc. (Lavipharm) invented this ideal intraoral FDDS. Thin, flexible, and quick‐dissolving film. Quick‐Dis™ provided in various packaging configurations, unit‐dose pouches to multiple‐dose blister packages. Film with a thickness of 2 mm have disintegration time 5 to 10 seconds & dissolving time, is around 30 seconds. Typical release profile of API is 50% released within 30 seconds and 95% within 1 minute. 45
  • 46. 10. Zydis technology Zydis is a unique freeze dried oral solid dosage form. Dissolves in less than 3 seconds. Drug is physically trapped in a water soluble matrix, and then freeze dried. Thirteen products are currently available based on zydis technology. In worldwide market, zydis formulations available for oxazepam, lorazepam, loperamide, and enalapril. 46
  • 47. Matrix contain excipients like 1] Polymers (e.g., gelatine, alginates, and dextrin) to provide strength and rigidity to tablets; 2] Polysaccharides (e.g.,mannitol and sorbitol) to impart crystallinity and hardness to the matrix and to improve palatability; 3] Collapse protectants (e.g, glycin) to prevent the product from shrinking in its packaging during manufacturing or storage; 4] Flocculating agents (e.g, xanthan gum and acacia) to provide uniform dispersion of drug particles; 5] Preservatives(e.g., parabens) to prevent microbial growth; 47
  • 48. 6] Permeation enhancers (e.g., sodium lauryl sulphate) to improve transmucosal permeability; 7] pH adjusters (e.g, citric acid) to optimize chemical stability; 8] Flavours and sweeteners to improve patient compliance and 9] water to ensure formation of porous units. In US, zydis products available- Claritin Reditab, Dimetapp Quick Dissolve, Feldene Melt, Maxalt-MLT, Pepcid RPD, Zofran FDT, and Zyprexa Zydis. 48
  • 49. 11. Frosta technology Patented by Akina. It utilizes core concept of formulating plastic granules and compressing at low pressure to produce strong tablets with high porosity. Process involves mixing the porous plastic material with water penetration enhancer and granulated with binder. Used for - aspirin, loratidine, caffeine, and folic acid, vitamins and dietary supplements. 49
  • 50. Superdisintegrants employed in ODT Super Commercially Mechanism of Special disintegrants available grades action comment Crosslinked Crosscarmellose® Swells 4-8 folds in Swells in two Cellulose Ac-Di-Sol®, < 10 seconds. dimensions. Nymce ZSX® Swelling and Direct Primellose®, wicking both. compression or Solutab®, Granulation Vivasol®, L-HPC Starch free. Crosslinked Crosspovidon M® Swells very little Water insoluble PVP Kollidon® and returns to and Polyplasdone® original size after spongy in nature compression but act so get porous by capillary action. tablet. 50
  • 51. Crosslinked Explotab® Swells 7-12 folds in Swells in three starch Primogel® < 30 seconds. dimensions and high level serve as sustain release matrix. Crosslinked Alginic acid Rapid swelling in Promote alginic NF aqueous medium or disintegration Acid wicking action. in both dry or wet granulation. Soy Emcosoy® Does not contain Polysaccharides any starch or Sugar. Used in Nutritional products. Calcium silicate Wicking action Highly porous, Light weight. 51
  • 52. Marketed product of MDTs Brand name Active ingredient Application company Claritin® Loratadine Antihistamine Scherig RediTabs® corporation Feldene Melt® Piroxicam NSAIDs Pfizer Maxalt® -MLT® Rizatritpan Migrane Merck benzoate Pepeid® ODT Femotidene Anti-ulcer Merck Zyperxa® Olazepine Psychotropic Eli Lilly Zofran® ODT Olandansetron Antiemetic Galaxo Smith kline Resperdal® M- Resperidone Schizophrenia Janssen Tab TM Klonopin® wafer Clonazepam Sedation Roche Imodium Istant Loperamide HCL Antidiarrheal Jannsen Melts Nasea OD Ramosetoron HCl Anti-emetic Yamanouchi Tempra Acetaminophen Analgesic Bristol-M Quicksolv® ters squibb 52
  • 53. Preformulation Studies 1. Bulk Density Formula Where : ρb - Bulk density, M- Weight of powder, and V- Volume of powder. 2. Tapped Density Formula ρt = M / Vt Where : ρt - Tapped density, M- Weight of powder, and Vt- Minimum volume occupied after tapping. 53
  • 54. 3. Compressibility Index Simplest way for measurement of flow of powder. Formula % C.I. = ρt – ρb/ρt x100 4. Hausner ratio Hausner ratio is an indirect index of ease of powder flow. Lower the value of Housner ratio better is the flow property. Formula Hausner ratio = ρt/ ρb 54
  • 55. Flow property % C.I. Hosner ratio Excellent ≤10 1.00-1.11 Good 11-15 1.12-1.18 Fair 16-20 1.19-1.25 Passable 21-25 1.26-1.34 Poor 26-31 1.35-1.45 Very poor 32-37 1.46-1.59 Very, very >38 >1.6 poor 55
  • 56. 5. Porosity Formula ε = ( 1 - ρapp / ρtrue) X 100 Where, ε- Porosity, ρapp- Apparent density, and ρtrue- True density. 6.Voide Volume Formula V = Vb - Vp Where, V- Voide volume, Vb- Bulk volume, and Vp- Tapped volume. 56
  • 57. 7. Angle of repose Formula ϴ = Tan-1 ( h / r ) Where, ϴ- Angle of repose, h- Hight of the heap, and r- Radius of the heap. Flow property Angle of repose (degrees) Excellent 25-30 Good 31-35 Fair- aid not needed 36-40 Passable- must agitate, 41-45 vibrate Poor 46-55 Very poor 56-65 Very, very poor >66 57
  • 58. Evaluation of Mouth dissolving 1. Thickness Measured using Vernier calipers. 2. Hardness Force required to break a tablet by compression in the radial direction. Pfizer hardness testers Monsanto hardness tester. 58
  • 59. 3. Uniformity of weight 20 tablets randomly take from lot and weighted individually to check for weight variation. Weight variation specification as per IP Average weight of tablet % Deviation 80 mg or less ±10 More than 80 mg but less than ±7.5 250 mg 250 mg or more ±5 59
  • 60. 4. In-vitro dispersion time test Drop a tablet in a beaker containing 50ml of sorrenson’s buffer pH 6.8 & time required for complete dispersion was determined. 60
  • 61. 5. Friability test Determined using Roche friability. Subjected to 100 revolutions (25rpm/minute). Formula f = (1- W0 / W) × 100 Where, f- Friability, W0- Weight of the tablets before, and W- Weight of the tablet after the test. 6. In vivo Disintegration time Time required for complete disintegration of tablets in oral cavity determined by administering tablets to 10 healthy volunteers. 61
  • 62. 7. Wetting time Tablet is placed on a piece of tissue paper folded twice and kept in a Petri dish (ID = 6.5 cm) containing 6 ml of water, and the time for complete wetting is measured. 8. Water absorption ratio This test performed as like wetting time Formula R = 10 ( Wa /Wb) Where, R- Water absorption ratio, Wb- Weight of tablet before water absorption, & Wa- weight of tablet after water absorption. 62
  • 63. 9. Dissolution test Dissolution study performed using USP II apparatus (paddal speed 50rpm). USP monographs dissolutions conditions should be followed in addition 0.1N HCl, pH 4.5 & 6.8 buffers should be evaluated. 10. Stability study As per ICH Q1A guidelines for accelerated studies. Tablets stored at 40±1ºC/75% ± 5% RH for 4 weeks. 63
  • 64. Afterword withdraw & analyse for physical characterization (visual defects, hardness, friability, disintegration, dissolution etc.) drug content. 64
  • 65. Promising Drugs to be incorporated In FDT Analgesics and Anti-inflammatory Agents Anti-Arrhythmic Agents Anti-bacterial Agents Anti-coagulants Anti-Epileptics Anti-Fungal Agents Anti-Gout Agents Anti-Hypertensive Agents Anti-Malarials Anti-Neoplastic Agents And Immunosuppressants Anti Protozoal Agents Anti-Muscarinic Agents Anti-Parkinson Agents 65
  • 66. Gastro-Intestinal Agents Histamine H,-Receptor Antagonists Stimulants Lipid Regulating Agents Local Anaesthetics Neuro -Muscular Agents Nitrates And Other Anti-Anginal Agents Nutritional Agents Opioid Analgesics Oral Vaccines Proteins, Peptides And Recombinant Drugs Sex Hormones Anti-Thyroid Agents Anxiolytic, Sedatives, Hypnotics And Neuroleptics Tj-Blockers 66
  • 68. References  Prashant B Pawar, “MOUTH DISSOLVING TABLET: A REVIEW”, International Journal of Herbal Drug Research, Vol I, Issue II;2011, Page no.- 22-29. Debjit Bhowmik, “Fast dissolving tablet: A review on revolution of novel drug delivery system and new market opportunities” Scholars Research Library, Der Pharmacia Lettre, 1 (2); 2009, Page no.- 262-276.  Alok Kumar Gupta, “Fast Dissolving Tablet- A Review”, The Pharma Innovation, Vol. 1(1); 2012, ISSN 2277-7695, Page no.- 1- 7.  V. Dinesh kumar, “A comprehensive review on fast dissolving tablet technology”, Journal of Applied Pharmaceutical Science, 01 (05); 2011, ISSN: 2231-3354, Page no.- 50-58.  A. Gupta, “Recent Trends of Fast Dissolving Tablet - An Overview of Formulation Technology”, International Journal of Pharmaceutical & Biological Archives, 1(1); 2010, Page no.- 1-10. 68
  • 69.  Velmurugan S., “Oral Disintegrating Tablets: An Overview”, International Journal of Chemical and Pharmaceutical Sciences, Vol.1 (2); Dec. 2010, Page no.- 1-12.  P. Ashish, “A Review- Formulation of Mouth Dissolving tablet”, International Journal of Pharmaceutical and Clinical Science, 1 (1); 2011, Page no.- 1-8.  Bhupendra G Prajapati, “A Review on Recent patents on Fast Dissolving Drug Delivery System”, International Journal of Pharm Tech Research CODEN( USA): IJPRIF ISSN : 0974-4304, Vol.1, No.3; July- Sept 2009, Page no.- 790-798.  Mukesh P. Ratnaparkhi, “Review On: Fast Dissolving Tablet”, Journal of Pharmacy Research, Vol.2, Issue 1; January 2009, Page no.- 5-12.  Tejvir Kaur, “Mouth Dissolving Tablets: A Novel Approach To Drug Delivery”, International Journal of Current Pharmaceutical Research, ISSN- 0975-7066, Vol 3, Issue 1; 2011, Page no.- 1-7.  Jaysukh J Hirani, “Orally Disintegrating Tablets: A Review”, Tropical Journal of Pharmaceutical Research, 8 (2); April 2009, Page no.- 161-172 69