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Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 14
CHAPTER 3.LITERATURE REVIEW
3.1 Current status and advantages of fast dissolving tablets
Fast dissolving drug delivery system are aimed at improving efficacy and bioavailability
of various existing drugs, as well as providing benefits of reducing dosing frequency,
minimizing side effect and enhanced patient compliance. Solid dosages forms that can be
dissolved in or suspended with water in mouth have a huge potential among the pediatric and
geriatric population [19].
In one of the studies, it has been shown that approximately 35 % of general
population, 30-40 % of elderly institutionalized patients and 18-22 % of all persons in long
term care facilities suffer from dysphagia [1]. Another study estimated around 50% of
population suffered from dysphagia [2]. In some cases such as motion sickness, sudden
episodes of allergic attacks, travelling patients, unavailability of water, swallowing of
conventional tablets is difficult. Geriatric or pediatric patients particularly experience these
difficulties. During the last decade, fast dissolving tablet technologies that makes tablets
disintegrate in the mouth without additional water intake have drawn a great deal of
attention.
The key advantages offered by the fast dissolving tablets are as follows:-
Provide good mouth feel.
Ease administration to pediatric, geriatric and psychiatric patients.
Rapid onset of action.
No need of water to swallow the dosage form, which provide ease of administration
during travelling.
Pre gastric absorption can result in improved bioavailability.
Free of the risk of suffocation due to physical obstruction when swallowed, thus
offering improved safety [20-23].
Accurate dosing as compare to liquids.
Allow ease of termination of therapy [24].
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3.2 Patented technologies used to manufacture fast dissolving tablet
3.2.1 Zydis Technology
The Zydis technology was patented by R.P Scherer. In the Zydis formulation the drug
is physically trapped in a matrix which is composed of two components. One is water
soluble mixture of saccharides and other is polymer. After the solution or dispersion is filled
in to blister cavities, than it is frozen in a liquid nitrogen freezing tunnel, solvent is than
removed to produce porous wafers. Due to fragile and light weighted unit, a special
peelable backing foil was used to package the Zydis unit. Water content in the final freeze
dried product is too low for microbe to grow, the Zydis formulation is self-preserving [25-
26].
3.2.2 OroSolve technology
ORASOLV technology (CIMA Lab) produced tablet by direct compression technique
at low compression force in order to minimize oral dissolution time [27]. It is slightly
effervescent tablet that rapidly dissolves in mouth. Concentration of effervescent mixture
usually employed is 20-25% w/w of total tablet weight. A pharmaceutical ingredient
incorporated in the tablet was in microparticle form. The microparticle may be prepared as
microcapsule. Microparticle form may be used to tast masking as well as to control the drug
release profile. The tablets produced are soft and friable and packaged in specially designed
pick and place packaging.
3.2.3 DuraSolv Technology
DuraSolv is CIMA’s second-generation fast-dissolving tablet technology. The key
ingredients are non-direct compression filler and a lubricant. The tablet have low friability of
about 2 % or less and hardness is at least about 15-20 Newtons. The disintegration time is
less than 60 seconds. The amount of non-direct compression filler is about 60-95% of the
total tablet weight. DuraSolv is so durable that it can be packaged in either traditional blister
packaging or glass vials. Diluents used have a high surface area, which leads to increase
dissolution rate. Due to the incorporation of high proportion of diluents the tablet to melt or
dissolve rather than disintegrate [28].
3.2.4 WOWTAB technology
WOWTAB technology (Yamanouchi Pharmaceutical Co. ltd., Japan.) employs
combination of low and high moldability saccharides to produce fast dissolving tablet using
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granulation and tableting technique [29]. In this technology saccharides were divided in two
groups: saccharides with high moldability and low moldability. The Low moldability
producing tablets with hardness 0-2 kg, while saccharides with high moldability producing
the tablets with hardness of more than 2 kg. When placed in the oral cavity it rapidly
becomes soft by absorption of saliva and disintegrates or dissolves within 15 to 20 seconds.
The wow tab product dissolves quickly in 15 s or less. Wowtab product can be pack in both
into conventional vials and blister packs [29].
3.2.5 Flashtab technology
Flashtab technology (Prographarm laboratories) includes granulation of excipients by
wet or dry granulation method. Two types of excipient (disintegrating & swelling agent)
were used in this technology. The tablets possess satisfactory physical resistance. These
tablets disintegrate with in one minute in oral cavity [30].
3.2.6 Flashdose technology
Flashdose technology (Fuisz corporation) consist of self-binding shearform matrix
termed as ‘’floss’’. This technology utilizes a unique spinning mechanism toproduce a floss-
like crystalline structure of sugar much like cotton candy. The speed of spinning is about
3000- 4000 rpm and the temperature gradient is about 180-2500 C. The produced floss
needs to be recrystallized to form freely flowing granules with self-binding properties. Two
techniques were used for recrystallization. One is by using crystallization enhancers and
other technique was using crystallization modifiers. The active drug is also incorporated in
crystalline sugar and compressed into a tablet. The final product has a very high surface area
for dissolution. It disperses and dissolves quickly once placed on the tongue. By changing
the temperature and other conditions during production, the characteristics of the product
can be altered greatly [31].
List of some patented products are shown in Table 3.1
Table 3.1 List of some patented product available in the market
Sr No Product Patented
technology
Name of the
company Composition
1 Claritin
Rediteb Zydis
R.P. Scherer/
Schering Plough,
Kenilworth, USA
Micronized loratidine (10
mg), citric acid, mannitol,
gelatin, mint flavor
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Feldene
Melt
Pfizer Inc, NY,
USA.
Piroxicam (10 or 20 mg),
mannitol, gelatin,
aspartame, citric anhydrous
Maxalt-
MLT
R.P.Scherer/Merck
& Co., NY, USA
Rizatriptan (5 or 10 mg),
mannitol,
gelatin,aspartame,
peppermint flavor
Pepcid
RPD
Merck & Co., NY,
USA
Famotidine (20 or 40 mg),
mannitol,
gelatin, aspartame
Zofran
ODT
R.P.Scherer/ Glaxo
Wellcome,
Middlesex,UK.
Ondansetron (4 or 8 mg),
mannitol,
gelatin, aspartame, methyl
paraben
sodium, propyl paraben
sodium,
strawberry flavour
2
Remeron
Soltab
Orasolv
CIMA/Organon,
GlaxoWellcome,
Middlesex, UK
Mirtazepine (15,30, or 45
mg),
mannitol, aspartame, citric
acid,cross povidone, avicel,
sodium bicarbonate, HPMC,
magnesium
stearate, povidone,
polymethacrylate, starch,
sucrose,orangeflavor
Tempra
FirstTabs
CIMA/Mead
Johnson, Bristol
Myers Squibb, NY,
USA.
Acetaminophen (80 or
160mg), mannitol (currently
available in Canada)
3 Nulev Durasolv CIMA/Schwarz Hyoscyamine sulphate
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Pharma (0.125mg), aspartame,
colloidal silicon dioxide,
cross povidone, mint flavor,
magnesium stearate,
mannitol, avicel
Zoming
ZMT
CIMA/ Astra
Zeneca,
Wlmington, USA.
Zolmitriptan (2.5mg),
mannitol, aspartame, citric
acid anhydrous, cross
povidone, avicel, sodium
bicarbonate, magnesium
stearate, colloidal silicon
dioxide, orange flavor
3.3 Approaches for fast dissolving tablets
Various approaches to formulate fast dissolving tablets can be possible, which are
discussed as under.
3.3.1 Lyophilization or Freeze drying
Freeze drying (Lyophilization) can be used to prepare tablets that have very light and
porous structure in to which saliva rapidly moves to disintegrate the lyophilized mass after it
is placed in mouth. The drug released form the freeze dried product instantaneously as the
highly porous structure dissolve or disintegrates rapidly when placed in mouth. The main
advantage of freeze drying method is that the entire process is carried out at non-elevated
temperature, which eliminates the adverse thermal effect that may affect the drug stability
during processing. The dissolution characteristic of drug may get enhanced as lyophilized
product imparts a glassy amorphous structure.
The freeze drying process is relatively time consuming and expensive manufacturing
process. Other drawbacks include fragility and poor stability during storage under stressful
condition such as higher temperature and humidity [32].The Zydis technology is the well-
known example of the freeze drying method. Quicksolve is a porous solid form obtained by
freezing the matrix composition dissolved in first solvent. Then second solvent was used to
remove the first solvent [33]. Corveleyn and Remon studied various formulations and
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process parameters by using hydrochlorthiazides as a model drug [34]. Lyoc is a porous
product, solid galenic form obtained by lyophilization of an oil-in-water emulsion placed
directly in blister pockets [35].
3.3.2 Molding
The major components of molded tablets are typically water soluble ingredients. In
this method the powder mixture is moistened with a solvent (usually ethanol and water),
and then the mixture is compressed into mould plates to form wetted mass (compression
molding). The wet mass is molded into tablets under pressures lower than those used in
conventional tablet compression. The solvent evaporates by air-drying. Molded tablet are
much less compact than compressed tablets, higher porous structure is created which
enhance the dissolution. The molded forms have also been prepared directly from a molten
matrix in which the drug is dissolved or dispersed or by evaporating the solvent from a drug
solution or suspension at ambient pressure. The major component in the dispersion matrix
is generally made from water-soluble sugars; molded tablets disintegrate more rapidly and
offer improved taste. Typically molded tablets do not have great mechanical strength [36].
By using nonconventional equipment and/or multistep process, FDTs with both
adequate mechanical strength and good disintegration have been prepared by molding
technique. As compared with FDTs prepared by freeze-drying, molded tablets can produced
more simply an efficiently at an industrial scale. Takeda (Osaka,Japan) has developed
compression molded mixtures containing an active ingredient, a carbohydrate, and
sufficient amount of water to moisten the surface of particle (37). After the wetted mass is
compressed at low pressure and subsequently dried, porous tablets with sufficient
mechanical strength can be obtained. The weight of this tablet can reach 1-2 g and
disintegration time up to 30-50 seconds. Molded tablet do not have great mechanical
strength. Erosion and breakage of molded tablet often occurs during tableting handling and
when blisters packets are opened.
3.2.3 Direct compression
Using conventional tablet press to make fast dissolving tablets is a very attractive
method, which offers low manufacturing cost and ease of technology transfer [38]. It has
other advantages such as commonly available excipients and limited number of processing
steps. High dose can be accommodating in these dosage forms. In direct compression
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method, disintegration and solubilization of tablet is based on single and combined action of
disintegrants, water soluble excipients and effervescent agents. However, tablet size and
hardness can affect the disintegrating efficiency of the disintegrating agent. Large and hard
tablets can take longer time to disintegrate. As a result, product with optimal disintegrating
properties often has medium- small weight and/or low physical resistance.
Many strategies have tried to achieve high porosity and adequate mechanical
strength using tablet press. In first approach, several granulation methods were tried to
obtained granules suitable for making FDTs. The second approach is to select special type of
excipients as the main component of FDTs. The third approach is to compress tablets at low
pressure and apply various after treatments to the soft tablets.
The three approaches are described in details below
3.2.3.1 Granulation methods
3.2.3.1.1 Wet granulation
Bonadeo et al. described a process of producing rapidly disintegrable, mouth soluble
tablets by wet granulation in a fluidized bed [39]. They found that even with effervescent
agents presented in the tablet with lower than 5%, similar quick disintegration time could be
achieved. Furthermore, they found that fast disintegration time could be achieved using
only the acid components of the effervescent couple. They used polyalcohol, 1-30% edible
acid, and an active ingredient as the dry mixture. This mixture was wet granulated with an
aqueous solution of water soluble or water-dispersible polymer (poly ethylene glycol,
carrageenan) which consist 1-10% of the final weight of the granule in the fluid bed.
Granules with high porosity and low apparent density were obtained. Tablets prepared by
this method rapidly disintegrated in 3-30 seconds in the saliva.
3.2.3.1.2 Dry granulation
Mehta PR et al. disclosed a method of preparing solid dosage form by dry
granulation technique for oral administration which disintegrates or dissolve rapidly in
mouth. The object of the invention is to provide a process for preparing rapidly
disintegrating dosage form by roller compaction or slugging for the active ingredient in
combination with other ingredients. The process involves three steps. In the first step, the
high-density flakes or slugs of either the mixture of active ingredient and other excipients by
means of roller compaction or slugging. In the second step, the obtained flakes or slugs are
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screened using oscillating granulator to obtained granules of desired size. In third step,
these granules are compressed in to tablet. The prepared tablets have hardness between 2-
15 kp and friability of less than 1% [40].
3.2.3.1.3 Spray drying
Spray-drying provides a fast and economical way of removing solvents and producing
highly porous, fine powders. Allen et al. produced a particulate support matrix for use in
forming fast-dissolving tablets by using spray-drying technique [41-44]. The component in
this particulate support matrix include supporting agents composed of two polypeptide
component of same net charge, a bulking agent (mannitol), and volatilizing agent. To
maintain the net charges of the polypeptide components, an acidifying or alkalinizing agent
may be included. The mixture of above components was spray dried to obtained porous
granules. The solubility of matrix was further increased when combined with a bulking
agent. A minimal amount of effervescent agent may be optionally included to further
accelerate the dissolution rate. A thin coating of polymeric material may also be applied to
keep the tablets intact during handling.
3.2.3.2 Excipients
3.2.3.2.1 Calcium salt
Dobetti has developed a formulation using insoluble inorganic excipients as the main
component for fast disintegrating tablet [45]. According to Dobetti’s patent, disintegration
of tablet in oral cavity depends on the quantity of the Disintegrants and in-soluble inorganic
excipient used. Disintegration also depends upon ratio of water soluble and insoluble
excipients. There are three major components in this formulation-
Substantially water insoluble components.
This group includes water-insoluble excipients, water in-soluble drugs (either coated or
uncoated), and water in-soluble lubricant and glidant.
Substantially soluble components
These include compressible sugars, flavouring agent, sweeteners, binders and
surfactant.
Disintegrants
Maize starch or modified starch, cross linked polyvinylpyrrolidone or sodium
carboxymethylcellulose.
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The most desirable amount of the substantially water insoluble components is about
72-92 (w/w) %. The disintegration time increases as the amount of insoluble components
decreases. The amount of active relative to substantially water-insoluble inorganic
excipients is most preferably 9:1 to 2:1. The components in the formulation were mixed in
the powder form and directly compressed into tablets. The disintegration time was found to
be 20 seconds and friability was about 2% or less.
3.2.3.2.2 Sugar based excipients
Sugar based excipients, such as sorbitol, mannitol, dextrose, xylitol, fructose,
maltose, isomalt, lactitol, starch hydrolysate, have been widely used as bulking agent
because of their high aqueous solubility and sweetness, pleasing mouth-feel and good taste
masking. Nearly all formulations for rapidly dissolving tablets incorporate some sugar
material in their formulations [2].
3.2.3.2.3 Disintegrants
Most fast dissolving tablet formulations use some type of disintegrants. Some
researchers use effervescent couples as their disintegrant, while others use a combination
of disintegrants. Dobetti summarized different types of non-effervescent disintegrants used
in the pharmaceutical area [45].
Starch and modified starches.
Cross-linked polyvinylpyrrolidone.
Modified cellulose such as cross-linked sodium carboxymethylcelluloses.
Alginic acid and sodium alginate
Microcrystalline cellulose
Methacrylic acid-divinylbenzene copolymer salts
3.2.3.2.3 Compaction and subsequent treatments
3.2.3.2.3.1 Sublimation
In sublimation technique, high porosity in tablets is achieved by using volatile
materials. Ingredients such as urea, camphor, thymol, ammonium carbonate, can volatilize
readily. When these materials are compressed in to tablets, they can be removed via
sublimation. Removal of volatile materials from the tablets generates porous structure.
Gohel M et al. have prepared mouth dissolving tablets of nimusulide using vacuum drying
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technique [46]. A residual amount of adjuvants in the tablet may generate deleterious effect
on patients [47].
3.2.3.2.3.2 Humidity treatment
Some investigations have shown that when an amorphous sugar is treated to go
through the humidification and drying process, it changes to crystalline state. This change
increases the tablet strength substantially.
Liu et al. disclosed a system for making fast dissolving tablets by humidity treatment
[48]. The patent uses water soluble polymers as binder solution. The process includes the
following steps-
(i) A water soluble polymer was used as a binder solution to granulate active
ingredients and other excipients, such as low moldability sugars (e.g. mannitol,
lactose, glucose).
(ii) The granules were than compressed in to tablets.
(iii) The tablets were humidified at relative humidity of about 50-100%.
(iv) Then the tablets were dried.
The hardness of the tablet was about 0.5-12 kilo pound and the in vivo disintegration time
was claimed to be about 1 to 40 seconds.
3.2.3.2.3.3 Sintering
Lagoviyer et al. disclosed a process that increased the tablet strength by sintering the
tablet components at high temperatures and re-solidify after temperature decreased
subsequently [49]. The various components in the formulation include bulk agents,
structure agents, solvent, and binding agents. The suitable structure agents should provid a
porous support structure allowing quick dissolution of the tablet in the mouth. These agents
include agar, gelatin, and albumen. The amount of gelatin ranged from approximately 1 to
3%. The preferred solvent is the mixture of ethyl alcohol and water in a ratio ranging from
1:1 to 1: 100.
The binder needs to melt at sintering stage, and form bonding among granules and
re-solidify as the temperature of the final sintering or heating step decreases. The heating
step was intended to melt the binding agent to create intra tablet bonds. The binding agents
were re-solidified as the temperature reduced to ambient temperature. The disintegration
time was found to be 3-60 seconds.
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3.4 Patent on fast dissolving tablets of various drugs
Table 3.2 discusses patents for various drugs by different investigators
Table 3.2 Patents on fast dissolving tablets using various drugs
No Investigator Drug Description Ref.
No
1 Norman E.
Jager et al.
Acetamenophen Patent described about a tablet
that rapidly disintegrates in
aqueous solution includes a
partially collapsed matrix
network that has been vacuum-
dried above the collapse
temperature of the matrix. The
matrix is preferably at least
partially dried below the
equilibrium freezing point of the
matrix. Vacuum drying the
tablet above its collapse
temperature instead of freeze
drying it. below its collapse
temperature provides a process
for producing tablets with
enhanced structural integrity,
while rapidly disintegrating in
normal amounts of saliva. The
tablet preferably carries a drug,
a gum, a carbohydrate, a
flavoring, a sweetener and
surfactant. The gum is
preferably acacia, guar,
xanthan, carrageenan or
tragacanth gum. The
[50]
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carbohydrate is preferably
mannitol, dextrose, sucrose,
lactose, maltose, maltodextrin
or corn syrup solids.
2 Khawla A et al. Ibuprofen The invention provides
composition and methods for
preparing fast dissolving tablets
of low hardness but good
physical stability at a very low
compression force, it comprises
a low melting point compound
that melts or softens at or
below 37 °C, a water soluble
excipient, and an active
ingredient. Tablet disintegration
time was found to be 10-30
seconds with excellent mouth
feel.
[51]
3 Caeiro R.M.J.
et al.
Domperidone The invention relates to fast-
water dispersible tablet
containing Domperidone,
auxiliary granulate (obtained by
wet granulation of maize starch
and D-mannitol,
microcrystalline cellulose, a
sweetner, and a flavouring
agent. Prepared tablets were
dispersing in water within 3
minutes, with hardness 3-6 kp
and friability of lowe than 1 %.
[52]
4 Janssen galanthaminehydrobromide Patent describes [53]
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Pharmaceutica galanthaminehydrobromide fast
dissolving tablet prepared using
spray dried carrier as a diluent
(lactose monohydrate and
microcrystalline cellulose) in
ratio of 75:25 and a disintegrant
using direct compression
technique.
5 Ahmed S.U. et
al.
Ondansetron Patent disclose formulation of
ondansetron orally
disintegrating tablets using at
least one water-dispersible
component or water-insoluble
cellulose derivative, a
component having a —CHOH
functional group, a
disintegrating agent and at least
one lubricant, such as
microcryastalline cellulose,
mannitol, crosspovidone and a
mixture of magnesium stearate,
sodium stearylfumarate and
colloidal silicon dioxide
respectively.
[54]
6 Venkatesh
G.M.
Ondansetron Investigation disclosed orally
disintegrating tablet containing
rapidly dispersing
microgranules, which comprised
a disintegrant and one sugar
alcohol or saccharide with a
particle size not more than 30
[55]
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micrometer.
7 Kang D.S. et al. Ondansetron Patent disclosed the
formulation of rapidly
disntegrable compositions of
Ondansetron or a
pharmaceutical acceptable salt
thereof and a alkalinizing agent.
Ondansetron salt has a
relatively lower solubility at
higher pH. Therefore, when the
composition was orally
administered, alkalinizing agent
lowers the solubility of
disintegrated ondansetron in
the oral cavity thereby masking
the bitter taste caused by
dissolution of ondansetron.
[56]
8 Platteeuw J.J.
et al.
Bio-active agent Orally disintegrating tablets
were made from insoluble
matrix-forming excipients
(silicified microcryastalline
cellulose), which is an intimate
mixture of colloidal silicon
dioxide with microcrystalline
cellulose, a disintegrant
(hydrxypropyl methyl cellulose).
Due to the presence of silicified
microcryastalline cellulose,
friability was found less than 0.2
%.
[57]
9 Kelly j. et al. Bioactive agent Patent disclosed the [58]
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preparation of fast-melt tablet
from the mixture comprising of
fast dissolving sugar alcohol,
disintegrant or osmotic agent
with at least one active agent by
direct compression method.
10 Castegini F. et
al.
Ibuprofen Fast dissolving tablets were
prepared by combining
ibuprofen, arginine, linear PVP
and an alkaline biocarbonate
and compressed. Prepared
tablets showed excellent
dissolution rate than compare
to commercially available
tablets.
[59]
11 Avci R et al. Fluriprofen The invention is related to orally
disintegrating tablets of
fluriprofen characterized in that
flurbiprofen particles are coated
with a coating agent, a pore
former and a surfactant.
[60]
12 Arora V.K. et
al.
Bioactive agent The investigation addressed the
drawbacks and problems
associated with currently
available technologies. In
present investigation fast
dissolving tablets wherein the
porosity was produced by in-
situ gas generation through
moister activation of the tablets
comprising effervescent
[61]
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mixture.
13 Lee D.H. et al. Megestrol The invention related to a fast-
dissolving megestrol tablet
preparation, which dissolve
quicker and provide convenient
dosage, and may exhibit the
effect of increasing the elution
and absorption of drugs so as to
thereby mask the bitter taste of
the drugs.
[62]
14 Clevenger J. et
al
Temazepam Patent disclosed preparation of
orally disintegrating tablet
comprising temazepam, a
binder polymer, rapidly-
dispersing microgranules
comprised the sugar alcohol
and/or saccharide in
combination with disintegrant.
Binder polymer was used to
form drug microgranule or may
be in the form of drug-layered
beads.
[63]
15 Kashid N. et al. Bioactive agent The invention related to
rapidly/orally disintegrating or
dissolving oral pharmaceutical
composition comprising one
active ingredient, polyol as a
filler, high amount of silicon
dioxide as cushioning agent,
disintegrating agent and
effervescent couple. Prepared
[64]
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tablets showed excellent
organoleptic properties.
16 M.H. Yoo et al. Amlodipine Investigation related to a
method for manufacturing fast-
dissolving tablet with improved
storage stability, as amlodipine
possess physical instability in
the presence of moister. The
tablets prepared according to
the present investigation
showed excellent results in
terms of appearance, content,
and dissolve quickly without any
discomfort.
[65]
17 Y. Fu et al. Placebo The investigation directed to a
pharmaceutical tablet capable
of melting rapidly in the buccal
cavity. Tablet comprised
plurality of highly plastic
granules, whereas granules
comprises of a porous, plastic
substance, a water penetration
enhancer, and a binder. The
prepared tablet showed good
hardness and friability.
[66]
18 H. Wadhwa Fexofenadine The patent disclosed a tasteless,
granular, directly compressible,
stable, fast dissolving complex
of a bitter tasting basic drug.
Complex was prepared by
reacting fexofenadine with an
[67]
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acidic polymer such as
carbomer.
19 L. Bellorini et
al.
Active drug The application disclosed oral
pharmaceutical composition
which are tasted in the mouth
during administration. Fast
dissolving tablets, chewable
tablet and effervescent
dispersions are exemplified.
Unpleasant taste of drug was
masked with cyclodextrin
without the conventional
complex formation using simple
granulation and dry blending.
[68]
20 M.W. Scheiwe
et al.
Active drug The invention related to an oral
dispersible tablet comprising
one filler selected from sugars
and sugar alcohol and
microcryastalline cellulose.
Tablets were prepared without
using any additional
Disintegrants..
[69]
21 J. Langridge et
al.
Sildenafil Patent disclosed fast dissolving
and taste masked sildenafil
dosage form comprising
sildenafil granules, which
comprised at least 45 % by
weight of a salt of sildenafil, a
solubilization inhibitor for the
salt and one or more
Disintegrants, alone or in
[70]
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combination in the form of
agglomerates.
22 P.C. Ubeda et
al.
Active agent Invention related to orally
disintegrating tablets obtained
by direct compression of dry
powder mix, said mixture
comprised of calcium silicate,
diluent and disintegrant. Tablet
disintegrated in the mouth in
less than 15 deconds.
[71]
23 P. Bagde et al. Active drug The investigation described
directly compressible composite
by co-processing a water-
soluble excipient and calcium
silicate. These composite
further compressed in to tablet
form.
[72]
24 J.M. Cornelius
et al.
Active drug The invention disclosed rapidly
disintegrating tablets through
the inclusion of titanium dioxide
material in combination with
other common tablet
components. Low surface area
boosts the ability to separate
quickly when introduced in to
user’s mouth.
[73]
25 A.K. Antarkar
et al.
LevocetrizineDihydrochloride The invention related to
preparation of resinates of
cetirizine or Levocetrizine
without the use of non-aqueous
solvent, which obviated the use
[74]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 33
of sophisticated packaging
machinery.
26 H. W. Bosch et
al.
Active drug (water soluble or
in-soluble)
In one of the embodiment of
invention the solid dosage form
prepared was fast-melt tablet.
Which comprised of pullulan,
active agent in nanoparticulate
size range, sugars and
plasticizer. Such tablets provide
the fast onset of therapeutic
effect.
[75]
27 E.D. Johnson
et al.
Apomorphine Hydrochloride In one of the embodiment of
the invention disclosed
preparation of fast dissolving
dosage form comprising of
gelatin as a carrier (up to 5%)
and other ingredients. Dosage
form comprised of a network of
active agent and water-
dispersible matrix forming
agent. Composition obtained by
subliming solvent.
[76]
28 V. Ahuja et al. Active agent Invention is directed to
pharmaceutical composition
comprising an open matrix
network carring an active agent.
Open matrix network comprised
of the levan and inulin.
[77]
29 D. Esra et al. Memantine The invention disclosed the
preparation of taste masked
orally disintegrating tablet of
[78]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 34
memantine using direct
compression method.
Memantine particle do not
require coating in order to taste
masking.
30 S.Y. Pechenov
et al.
Proteins The investigation related to the
rapidly disintegrating tablets of
proteins. Preparation comprised
a mixture of lipase, amylase,
protease and other excipients.
[79]
3.5 Work done on fast dissolving tablets of various drugs
Fast dissolving tablets developed by various researchers using different methods and
excipients. Table 3.3 focuses on design and development of fast dissolving tablets for
particular drug along with polymer composition, method used and core conclusion.
Table 3.3 Work done on fast dissolving tablets
No Investigator Drug Method Inference Ref
1 Y. Nakano
et al.
Pioglitazone Physical
taste
masking and
gustatory
masking
Study aimed to evaluate the
taste and mouth feel of
orally disintegrating tablets.
Gustatory masking
significantly suppresses both
the bitter ness and
astringent, which improve
the overall palatability of
formulation.
[80]
2 Y. Iwao
et al.
Ethanzamide Direct
compression
Study aimed to predict the
functionality and
mechanism of
disintegration. Water
absorption ratio of
[81]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 35
disintegranthad strong
negative correlation with
peak time and maximum
available surface area
3 S. Sano et
al.
Placebo Wet
granulation
along with
microwave
treatment
Hardness of the microwave
treated tablet was increased
with decrease in
disintegration time than
compare to microwave
untreated tablets.
[82]
4 J. Sruti et al. Cefuroximeaxetil Combination
of melt-
granulated
dispersion
and surface
adsorption
technique
Gelucire 50/13 plays a
significant role in
enhancement of drug
solubility and dissolution.
Sylysia 350 improved the
dissolution rate by
increasing the surface area.
[83]
5 K. Saroha et
al.
Amoxicillin
trihydrate
Direct
compression
Tablets prepared with blend
of crosscarmellose sodium
(60 mg) showed better
disintegration properties as
well as percentage drug
release.
[84]
6 Z. Ramtoola
et al.
Placebo Direct
compression
using central
composite
design
Compression force and
tablet diameter were
observed to have a
profound and interactive
effect on the characteristic
of orodispersible tablets.
Tablet with diameter 15 mm
and compression pressure
[85]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 36
of 15 kN was optimized.
7 V. Rana et
al.
Metoclopramide Direct
compression
Presence of Ca2+ that builds
intra and/or inter
cross-linked bridges in the
CaCOG or CaCEG, supported
water transporting
system even when the
aqueous channels in the
FDTs were
blocked. Overall, the
findings pointed CaCOG and
CaCEG could be
the superdisintegrants that
provides FDTs with
sufficient mechanical
strength with lowest DT.
[86]
8 M. A. A.
Masum et
al.
Ibuprofen Melt
dispersion
technique
Solid dispersions were
prepared using macrogol
4000 and 6000. Solid
dispersions containing
macrogol 6000 in ratio of
1:1.5 showed higher drug
release.
[87]
9 N. Jain et al. Ciprofloxacin Kneading
technique
Tablets containing
crosspovidone (40%) exhibit
quick disintegration time
than compare to other
super Disintegrants.
[88]
10 D.R. Rane
et al.
Albendazole Direct
compression
Formulation containing 5 %
crosspovidone and 20 %
microcryastalline cellulose
[89]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 37
was considered to be best
formulation.
11 T. Sugiura
et al.
Famotidine Taste
masking
using
suspension
spray
coating
In present investigation
physical masking by spray-
coating famotidine with
ethyl cellulose versus
organoleptic masking with
added sweetener and
flavour. , the combination of
both taste-masking methods
was most effective for
improving palatability and
VAS scores were similar to
those of placebo ODTs
[90]
12 M. E. Badry
et al.
Meloxicam Spray drying The microparticles prepared
at a ratio of 1:4
(drug/Gelucire)
exhibited a 4-fold higher
anti-inflammatory activity
on the paw edema of rats in
comparison to the drug
alone. Spray drying
technique was found to be
promising for preparation of
solid dispersion.
[91]
13 S. Itai et al. Placebo Wet
granulation
along with
microwave
treatment
Results demonstrated that
swelling phenomenon
occurred when the ratios of
silicon dioxide and absorbed
water in tablet were
appropriate.
[92]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 38
The tablet hardness as well
as disintergartion time for
all microwave-treated
tablets was
greater than that for non-
treated tablets. The effects
of several variables on the
physical tablet properties
were evaluated using a two-
factor full factorial
experimental design, and
then further optimized.
14 R. K. Nayak
et al.
Lornoxicam Direct
compression
Tablets containing
crosspovidone (4%) showed
least disintegration time
with 99 % drug release
within 12 min.
[93]
15 H. Chander
et al.
Ramipril Direct
compression
using
effervescent
material
Fast dissolving tablets with
sodium bicarbonate:
mannitol (1:3) showed more
release and least
disintegration time.
[94]
16 P.P.
Sawarikar
et al.
Isoxsuprine
Hydrochloride
Kneading
and co-
precipitation
Formulation containing Ac-
Di-Sol (6%) showed
complete drug release with
least disintegration time.
[95]
17 V. Bhardwaj
et al.
Amlodipine
Besylate
Sublimation
method
Formulation prepared with
6% Ac-Di-Sol and 10 %
camphor showed least
disintegration time and
faster dissolution.
[96]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 39
18 S.G. Late et
al.
Granisetron Direct
compression
with
response
surface
approach
In the present study, higher
concentration of β
cyclodextrin was found to
improve tablet hardness
without increasing the
disintegration time. Thus, β
cyclodextrin is proposed as a
suitable diluent to achieve
fast disintegrating tablets
with sufficient hardness.
[97]
19 A.S.
Kulkarni et
al.
Olanzapine Kneading
method and
direct
compression
Investigation concluded that
the combination of 2-
hydroxypropyl-beta
cyclodextrin and
superdisintegrant in
formulation showed
excellent result. It gave
faster release and
enhancement in the
dissolution rate.
[98]
20 T.Y.
Puttewar et
al.
Doxylamine
succinate
Ion
exchange
resin
It was concluded that
pharmaceuticals complexed
using ion exchange resins
have shown improved
organoleptic performance of
pharmaceuticals and better
patient compliance. The use
of cation exchange resin
offers good taste masking of
doxylamine
[99]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 40
succinate and its
formulation into
orodispersible table offers
advantages over
conventional tablet.
21 A.R.
Madgulkar
et al.
Tramadol HCl Direct
compression
with ion
exchange
resign
In this work bitter taste of
drug was masked by ion
exchange resin complex
with Tulsion335. The
statistical model were
validated and successfully
used to optimize taste
masked tablet with
adequate mechanical
strength and rapid
disintegration.
[100]
22 G. Chaulang
et al.
Furosemide Kneading
method
In study solid dispersion of
furosemide in SSG in ratios
of 1:1 and 1:2 by kneading
method was prepared.
Tablets containing the solid
dispersion were formulated
and their dissolution
characteristics compared
with commercial furosemide
tablets.
[101]
23 A. Kalia et
al.
Oxcabazepine Direct
compression
using solid
dispersion
technique
Oxcarbazepine solid
dispersions with PVP K-30 in
1:2 ratios maximum drug
release. The results
compared for both the
[102]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 41
technologies showed that
the oxcarbazepine tablets
prepared using solid
dispersion technology was
found to have good
technological properties and
satisfying and reproducible
drug dissolution profiles.
24 N.G. Rao et
al.
Chlorthalidone Direct
compression
using
cogrinding
and solid
dispersion
technique
Formulation containing
polyvinyl pyrrolidone K-12
solid dispersion showed
maximum drug release than
the chlorthalidone polyvinyl
pyrrolidone K-12 co-grinding
method.
[103]
25 D. N. Kumar
et al.
Fexofenadine Effervescent
method
The formulation containing
8% w/w of crospovidone
and mixture of 24% w/w
sodium bicarbonate, 18%
w/w of anhydrous citric acid
emerged as the best based
on the in vitro drug release
characteristics compared to
conventional commercial
tablet formulation.
[104]
26 P. V. Swamy
et al.
Pheniramine
maleate
Effervescent
method
Formulation containing 4%
w/w crospovidone and
mixture of sodium
bicarbonate and tartaric
acid emerged as the overall
best formulation in terms of
[105]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 42
rapid release and
disintegration.
27 S. R.
Devireddy
et al.
Levocetirizine
hydrochloride
Wet
granulation
and
kneading
method
Tulsion-335, Indion-204 and
poly kyron T-134 cation
exchange resins were used
as taste-masking agents.
Prepared tablets were
evaluated for different
tablet parameters.
[106]
28 T. K. Giri et
al.
Diazepam Wet
granulation
using solid
dispersion
Tablets which were
prepared with PEG-4000
alone at the lowest
concentration disintegrated
in the shortest time (32.12
s) and released 85% of the
drug most rapidly (11.03
min), formulations were
optimized using 32 factorial
design.
[107]
29 J. Singh et
al.
Meloxicam Wet
granulation
Results showed that
presence of a
superdisintegrant and
mannitol is desirable for
orodispersion. Optimized
formulation showed rapid
drug release and
disintegration.
[108]
30 J. Madan et
al.
Aloe vera gel Freeze
drying
The results of multiple
regression analysis revealed
that in order to obtain fast
dissolving tablets of the aloe
[109]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 43
vera gel, an optimum
concentration of mannitol
and a higher content of
microcrystalline cellulose
should be used
31 S. G. Late et
al.`
Granisetron Direct
compression
Results of multiple linear
regression analysis revealed
that concentration of
calcium silicate had no
effect; however
concentration of lubricant
was found to be important
for tablet disintegration and
hardness
[110]
32 P.S. Zade et
al.
Tizanidine
hydrochloride
Mass
extrusion,
Direct
compression
and
sublimation
Tablets prepared by
addition of
superdisintegrant has less
disintegration time than
those prepared by
sublimation method alone
[111]
33 S. Furtado
et al.
Famotidine Sublimation Tablets prepared with
subliming agent along with
superdisintegrant showed
good dissolution profile.
[112]
34 Mohapatra
et al.
Metformin Direct
compression
Tablet prepared with
RX1500 showed erosion
behaviour rather than
disintegration.
Incorporation of lactose
cause burst release.
[113]
35 Y. Kuno et Placebo Direct The oral disintegration time [114]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 44
al. compression of the tablets containing talc
was not changed despite of
an increase in hardness. The
water absorption rate of the
tablets containing talc was
much faster. The surface
free energy measurement
showed that the polarity of
the tablet components
containing talc was
remarkably increased by
heating.These results
indicate that a more
hydrophilic surface might be
attained by heating the talc.
Consequently, talc was
demonstrated to be the
most desirable lubricant for
the preparation of OD
tablets based on the
principle of the phase
transition of sugar alcohol.
36 S. H. Jeong
et al.
Dextromethorphan Fluidized
bed coating
As the particle size of resins
increased, the drug loading
and release rate decreased
due to the reduced effective
diffusion coefficient and
surface area. Higher coating
level decreased the release
rate further. In contrast to
EC, Kollicoat SR30D coated
[115]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 45
particles could be
compressed into tablets
without any rupture or
cracks on the coating
37 I.M. Patel et
al.
Etoricoxib Sublimation
method
A 32 full factorial design was
applied to investigate the
combined effect of
variables; amount of
menthol and crospovidone.
The result of multiple
regression analysis indicated
that for obtaining for fast
dissolving tablet optimum
amount of menthol and
higher percentage of
crospovidone should be
used.
[116]
38 R.S.
Masareddy
et al.
Clozapine Direct
compression
and
sublimation
method
The formulations showed
disintegration time in the
range of 25 to 35 s.
Comparative evaluation of
two methods showed direct
compression method was a
better alternative to
sublimation method as its
formulations rapidly
disintegrate in oral cavity.
Kinetic studies indicated
that all the formulations
followed first order release
with diffusion mechanism
[117]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 46
39 Y. C. Shen
et al.
Olanzapine Direct
compression
designed an orally
disintegrating tablet of
olanzapine to dissolve
rapidly upon contact with
saliva also described a manic
patient who has an
esophageal stricture and
chronic pharyngitis, two
conditions that impede the
swallowing of medications.
She was successfully treated
for her mania with this
orally disintegrating
formulation
[118]
40 B. J.
Mohammad
et al.
Carbamazepine Co-grinding
technique
Comparison of the
dissolution of the drug from
its co-grounds with that of
the unground drug. The
percentage of drug
dissolved during the first 30
min (% D30), for the ground
and co-ground drug was 75-
95.
[119]
41 S. Malke et
al.
Oxcarbazepine Wet
granulation
method
An effective, pleasant
tasting and stable
formulation containing 12%
Ac-Di-sol, 25% Avicel PH 102
and 8.5% starch as a binder
was found to have a good
hardness and rapid drug
release. The drug release
[120]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 47
was found to be comparable
to the marketed dispersible
tablet.
42 A. Modi et
al.
Valdecoxib Kneading
method
Dissolution of valdecoxib
improved significantly in
solid dispersion products
(<85% in 5 minutes). Tablets
containing solid dispersion
exhibited better dissolution
profile than commercial
tablets. Thus, the solid
dispersion technique can be
successfully used for
improvement of dissolution
of valdecoxib
[121]
43 I.S. Ahmed
et al.
Ketoprofen Freeze
drying
technique
The solubility and
dissolution rate of poorly
water-soluble ketoprofen
was improved by preparing
a lyophilized tablet of
ketoprofen using freeze-
drying technique.
[122]
44 M. Cirri et
al.
Flurbiprofen Direct
compression
All formulations containing
drug-cyclodextrin systems
gave a higher drug dissolved
amount than the
corresponding ones with
drug alone. In particular,
only tablets containing the
drug kneaded with methyl-
beta-cyclodextrin or co-
[123]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 48
lyophilized with beta-
cyclodextrin and spray-dried
lactose as the only excipient
satisfied the requirements
of the Food and Drug
Administration (FDA) for
rapid dissolving tablets,
allowing more than 85%
drug to be dissolved within
30 minutes possibility of
reducing drug dosage and
side effects.
45 C.
Francesco
et al.
Piroxicam The formation of solid
solutions improved the
dissolution rate and the
apparent drug solubility.
The microparticles
containing more than 50%
(m/m) of piroxicam did not
show mucoadhesive
properties. The delivery
system made of piroxicam
and EuLNa in the ratio
70/30% (m/m) appears to
be the most promising
because it contains the
lowest amount of polymer
able to confer
mucoadhesive properties
and increase apparent drug
solubility
[124]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 49
46 E.C. Rasetti
et al.
Piroxicam An open-
label,
randomized,
single dose,
crossover
study
The 90% confidence
intervals of the ratios of
means C(max), AUC(0-t),
AUC(0-infinity) and T(1/2) all
fell within the acceptance
range of 0.8-1.25,
demonstrating the
bioequivalence of the two
formulations. Although the
bioavailability of the two
formulations was similar,
the administration of
piroxicam as a freeze-dried
tablet gave a much faster
absorption rate during the
first hour after dosing than
the capsule formulation.
This faster absorption is an
obvious advantage for the
treatment of acute episodes
of pain.
[125]
47 B. S.
Kuchekar
Salbutamol
sulphate
Wet
granulation
method
In the present work, mouth
dissolving tablets of
salbutamol sulphate was
formulated. Formulations
were prepared by factorial
design technique. Different
disintegrates were used to
formulate fast dissolving
tablets.
[126]
48 J. K. Lalla et Rofecoxib Ball milling The fast dissolving tablet [127]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 50
al. technique composition with 25 mg
equivalent rofecoxib
showed complete release of
rofecoxib in 12 min as
compared to 20% drug
release from the
conventional release
marketed tablets during the
same period.
49 A.A.
Shirwaikar
et al.
Atenolol Dry
granulation
method
Fast disintegrating tablets
were formulated using
croscarmellose sodium (Ac-
di-sol), Polyplasdone XL and
Explotab. All the
superdisintegrants were
used at different
concentration levels to
assess their efficiency and
critical concentration level.
[128]
50 M. Valleri et
al.
Glyburide Direct
compression
and solid
dispersion
technique
larger sized solid dispersions
(20–35 mesh, i.e., 850–500
mm) of micronized
glyburide in polyethylene
glycol 6000 prepared by the
cofusion method gave the
best results, with a 135%
increase in drug dissolution
efficiency at 60 min.
Moreover, the glyburide
dissolution profile from the
newly
[129]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 51
developed tablets was
clearly better than those
from various commercial
tablets at the same drug
dosage.
51 D. J. Drooge
et al.
Diazepam Freeze
drying
Study related to anomalous
dissolution behavior of
tablets consisting of sugar
glass dispersions. The
release of diazepam and
sugar carrier was
determined to study the
mechanisms governing
dissolution behavior.
[130]
52 M. Gohel et
al.
Nimesulide Wet
granulation
and
sublimation
The results of multiple linear
regression analysis revealed
that for obtaining a rapidly
disintegrating dosage form,
tablets should be prepared
using an optimum
concentration of camphor
and a higher percentage of
crospovidone. Sublimation
of camphor from tablets
resulted in superior tablets
as compared with the
tablets prepared from
granules that were exposed
to vacuum.
[131]
53 M. Mrunali
et al.
Nimodpine Study related to design of
nimodipine tablets with fast
[132]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 52
in vitro release rates using
nimodipine-modified gum
karaya co-grinding mixtures.
Co-grinding mixtures of
nimodipine and gum karaya
were also prepared to
highlight the efficiency of
modified gum karaya
54 S. Simone
et al.
Ibuprofen Direct
compression
An optimum tablet
formulation, containing 34%
mannitol and 13%
crospovidone, provides a
short wetting time of 17 s
and a sufficient crushing
strength of 40 N. In
conclusion, fast dispersible
tablets with acceptable
hardness and desirable taste
could be prepared within
the optimum region.
[133]
55 H. Sunanda
et al.
Ethenzamide Direct
compression
and wet
granulation
Tablet properties such as
porosity, tensile strength,
wetting time and
disintegration time were
evaluated and the
formulation and
disintegration time of the
tablets were elucidated.
Formulation and
preparation conditions were
optimized using polynomial
[134]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 53
regression or artificial neural
network.
56 M. De Kerf
et al.
Biopolymers Irradiation
treatment
The irradiation treatment
caused fragmentation of the
amylopectin fraction.
Irradiation modified the
different starches
thoroughly, showing
remarkable differences in
disintegration properties
after X-ray treatment and e-
beam modification. The e-
beam modification resulted
in significantly higher
disintegration times of the
tablets.
[135]
3.6 Work done on fast dissolving tablet of anti-emetic drugs
Table 3.4 focuses on the work done on fast dissolving tablet of various anti-emetic
drugs
Table 3.4 Work done on fast dissolving tablet of various anti-emetic drugs
No Investigator Drug Method Inference Ref
1 S.S.
Deshmukh
et al.
Chlorpromazine
Hydrochloride
Direct
compression
Among all the
formulatios, tablet
containing
crosspovidone and
sodium starch glycolate
in the ratio of 1:1 Was
found to br promising in
terms of rapid drug
release and
[136]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 54
disintegration.
2 Nimisha et
al.
Meclizine Sublimation Disintegration time of
tablets prepared by
superdisintegrant
addition
weresignificantly less
(P < 0.05) than prepared
by sublimation technique
hence. The physical
properties of the
prepared tablets did not
show any significant
variations (P > 0.05) and
were found to have good
physical integrity
[137]
3 B. S. Patil
et al.
Granisetron HCl Direct
compression
The formulation
containing
croscarmellose sodium
showed superior in vitro,
in vitro dispersion time
and drug release, as
compared to other
formulations. Tablet
showed good dissolution
efficiency and rapid
dissolution
[138]
4 S. A.
Randale et
al.
Metoclopramide Direct
compression
and extrusion
precipitation
The complex having
drug-polymer ratio of 1:
2 shows significant taste
masking, confirmed by
drug. Prepared tablets
[139]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 55
showed rapid
disintegration in oral
cavity.
5 H. Goel et
al.
Metoclopramide Co- proceed
granules
Results revealed that
system consisted of
chitosan- alginate:
glycine and chitin
showed minimum water
sorption time and
maximum pore radius.
[140]
6 S. B.
Shrishand
et al.
Prochlorperazine
maleate
Direct
compression
Tablets containing
crosscarmellose and
cross povidone in
combination showed
rapid disintegration and
dissolution.
[141]
7 R. Dahima
et al.
Metoclopramide Direct
compression
Taste masked
tabletsshowed that more
than 85% of the drug
release within 10 min.
Thus, results conclusively
demonstrated successful
masking of taste and
rapid disintegration of
the formulated tablets in
the oral cavity.
[142]
8 S. B.
Mahamuni
et al.
Promethazine HCl Direct
compression
and mass
extrusion
Taste masked tablets
showed fast
disintegration and
pleasant mouth feel.
[143]
9 S. Sharma Promethazine Direct The optimized tablets [144]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 56
et al. theoclate compression prepared with an
optimum amount of
cyclodextrin, camphor
and crospovidone
showed rapid
disintegration and drug
release.
10 D.
Nagendra
et al.
Granisetron
Hydrochloride
Effervescent
method
Formulation containing
8% w/w of
croscarmellose sodium
and blend of 24% w/w
sodium bicarbonate, 12
% w/w of anhydrous
citric acid and 12 %w/w
tartaric acid emerged as
the overall best
formulation based on
the in vitro drug release
characteristics.
[145]
11 N. Vaja et
al.
Prochlorperazine
maleate
Direct
compression
Formulation containing
combination of sodium
starch glycolate and
crospovidone in
optimized showed rapid
drug release and
disintegration.
[146]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 57
3.7 Work done on fast dissolving drug delivery of domperidone
Table 3.5 focuses on the work done by various researchers on domperidone fast
dissolving system using various methods and excipients
Table 3.5 Work done on fast dissolving drug delivery system of domperidone
No Investigator Formulation Method Inference Ref
1 S. Patra et
al.
Mouth
dissolving
tablet
Direct
compression
The formulation containing
6% w/w concentration of
crospovidone was
considered to be the best
formulation, which showed
rapid drug release and
disintegration.
[147]
2 S. M. Assaf
et al.
Orally
disintegrating
tablet
Direct
compression
using solid
dispersions
Drug release from solid
dispersions was pH
dependent; showing higher
release rates at pH 6.8 than
at lower pH values. The
controlled-release ODT
resulted in 47% drug
release in 0.1N HCl, with
the rest of drug released at
pH 6.8.
[148]
3 E. A. Essa et
al.
Solid
dispersions
Solvent
evaporation
Some ternary P188
combinations showed a
better enhancement in
drug dissolution compared
to the optimized P188
binary system. This would
present a potential of
[149]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 58
increasing oral
bioavailability of
Domperidone by increasing
its dissolution rate and by
inhibiting its pre-systemic
metabolism by the
presence of P188.
4 D. S.
Ghodke et
al.
Inclusion
complex
Ultra
sonication
Drug content confirms that
ultra-sonication is one of
the efficient methods to
prepare inclusion complex.
Dissolution data of inclusion
complexes also indicated
that there is 1.4 folds
increase in dissolution as
compared to pure drug
[150]
5 H. Goel et
al.
Fast
disintegrating
tablet
Direct
compression
The predicted model
showed that disintegration
time of FDTs to be directly
correlated with powder
characteristics and
inversely correlated with
tablet crushing strength.
These observations
indicated the versatility of
the mathematical model in
predicting the
disintegration time of FDTs
by evaluating the selected
characteristics of the
powder blends without
[151]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 59
actually preparing the FDTs.
6 H. Goel et
al.
Fast
disintegrating
tablet
Direct
compression
with central
composite
design
The data revealed that
optimized domperidone
FDTs were better than
domperidone FDTs
containing croscarmellose
or crospovidone. Hence,
novel excipients
combination can be used
for delivery of water
insoluble drugs in place of
superdisintegrants.
[152]
7 B. A.
Chavan et
al.
Melt-in-mouth
tablet
Direct
compression
using inclusion
complex
Tablets containing
optimized multicomponent
inclusion complex
(Domperidone/ β-CD/ citric
acid/PVP K40) release more
than 80 % drug in 16 min.
[153]
3.8 Work done on fast dissolving drug delivery of ondansetron HCl
Table 3.6 focuses on the work done by various researchers on ondansetron HCl fast
dissolving system using various methods and excipients.
Table 3.6 Work done on fast dissolving drug delivery system of ondansetron HCl
No Investigator Formulation Method Inference Ref
1 H. Goel et
al.
Orodispersible
tablet
Direct
compression
Result showed that
disintegration time of
optimizedondansetron HCl
ODT prepared using glycine-
chitosan mixture was not
[154]
Bhatt S.O. Literature review
K. B. I. P. E. R. Kadi Sarva Vishwavidyalaya Page 60
significantly different form
ODT prepared using
crosscarmellose sodium or
crosspovidone.
2 P. K. Bhoyar
et al.
Orodispersible
tablet
Direct
compression
and
complexation
Taste masked ODT of
ondansetron HCl with rapid
disintegration and drug
release was prepared.
[155]
3 R. Sheshala
et al.
Orally
disintegrating
tablet
Wet
granulation
technique
It was concluded that, a cost
effective ondansetron orally
disintegrating tablet was
successfully prepared with
acceptable hardness,
desirable taste and rapid
disintegration in the oral
cavity
[156]
4 J.P.
LeBourgeois
et al.
Orally
disintegrating
tablet
Freeze drying In was concluded that,
Ondansetron ODT 8 mg is
effective in the treatment of
radiotherapy-induced emesis
and nausea and provides an
effective alternative to the
conventional ondansetron
tablet.
[157]
5 S. Khan et
al.
Rapid-
disintegrating
tablet
Direct
compression
and
precipitation
method
Results conclusively
demonstrated successful
masking of taste and rapid
disintegration of the
formulated tablets in the oral
cavity.
[158]
Preparation of Fast Dissolving Tablet (FDT)
1. Melting point
2. Identification of compound (FT-IR)
3. Saturation solubility study
4. Spectroscopic analysis
5. Chromatographic analysis
Enhancement of dissolution by solid dispersion technique
Design & development of FDT with different SD’s
Identification of best SD ratio
Optimization of FDT by DC using optimized SD ratio.
Variables
Superdisintegrating agent
Superdisintegrating agent conc.
Diluent concentration
Design & development of FDT by effervescent method
using optimized SD ratio
Variables
Effervescent agent conc.
Super disintegrating agent conc.
Domperidone
Pre formulation study
Ondansetron HCl
Taste masking of Ondansetron HCl by extrusion
technique & preparation of drug polymer
complex (DPC)
Optimization of FDT by DC using optimized DPC
Variables
Superdisintegrating agent concentration
Diluent ratio
Design & development of FDT by sublimation
tech. using optimized DPC
Variables
Conc. of camphor
Conc. Diluent
Selection of best formulation
Characterization In- vitro
In- vivo
Stability study
Conclusion
PLAN OF WORK