CHAPTER 3.LITERATURE REVIEW -...

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].



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



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



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



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



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



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



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.



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



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.



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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]



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


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]



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]



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]



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]



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]



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]



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]



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]



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


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]



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]



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]



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.


compression

and extrusion

precipitation

The complex having

drug-polymer ratio of 1:

2 shows significant taste

masking, confirmed by

drug. Prepared tablets

[139]



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.


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]



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


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


combination of sodium

starch glycolate and

crospovidone in

optimized showed rapid

drug release and

disintegration.

[146]



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]



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]



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]



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

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