International Journal of Progressive Pharmacy Vol.

1 Isuue 1

International Journal of Progressive Pharmacy

(A Peer-Reviewed Journal)
www. thesapience.in

ISSN 2454-1737
Review article

FAST DISSOLVING TABLETS OF POORLY SOLUBLE DRUGS: PREPARATION,

CHARACTERIZATION AND EVALUATION: AN OVERVIEW
Tiwari Reshu, Singh Satya P, Kushwaha Poonam, Usmani Shazia

Faculty of Pharmacy, Integral University, Lucknow 226026.

Received: 18 Mar 2015 Revised: 29 Mar 2015 Accepted: 01 Apr 2015

ABSTRACT: Drug delivery systems are becoming increasingly sophisticated as pharmaceutical

scientists acquire a better understanding of the physicochemical and biochemical parameters pertinent
to their performance. Fast-dissolving drug-delivery systems (FDDS) were first developed in the late
1970s as an alternative to tablets, capsules, and syrups. Products of FDTs technologies entered into the
market in the 1980. This has encouraged both academia and industry to generate new orally
disintegrating formulations and technological approaches in this field. At present 40% of the drugs in
the development stages and approximately 60 % of the drugs are poorly soluble. The poor solubility of
drugs is a big challange for industry, for the development of the solid dosage form drugs. Drugs having
slow dissolution rate show the incomplete absorption and low bioavailability when orally administered.
Various technologies are applied for the enhancement of solubility such as micronization technology,
solid dispersion technology, complexation technology etc. The ability to deliver poorly soluble drugs
will grow in significance in the coming years as NCEs are relied upon for a larger share of the revenue
within the pharmaceutical market by the pharmaceutical companies. Generic drug manufacturers will
also need to employ economically efficient methods for the delivery of poorly soluble drugs in order to
maintain a competitive edge and sufficiently compete as profit margins shrink in this price-sensitive
industry.

Keywords: Bioavailability, dissolution rate, fast-dissolving drug-delivery system, poorly soluble drugs.

INTRODUCTION:

1. Fast dissolving Drug Delivery System comparison to many other routes (Valleri et al.,
2004)
For most therapeutic agents used to produce
systemic effects, the oral route represents the perfect The conventional dosage forms (tablet and capsule)
way of administration and having several have wide acceptance up to 50-60% of total dosage
advantages and high patient compliance in forms. Tablet is still most popular conventional
dosage forms existing today because of easy self
Address for Correspondance:
Reshu Tiwari administration, compact in nature, easy to
Faculty of Pharmacy, Integral University, Lucknow manufacture and it can be deliver in accurate dose.
Contact: 09451036956 The problem of swallowing is common
Email id- reshu328790302@gmail.com,
phenomenon in geriatric patient due to fear of

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International Journal of Progressive Pharmacy Vol. 1 Isuue 1

choking, hand tremors, dysphasia and in young Rapid dissolution rate and absorption of the
individuals due to underdeveloped muscular and drug, which will produce quick onset of
nervous systems and in schizophrenic patients action.
which leads to poor patient compliance. Difficulties Bioavailability can be increased due to
in swallowing of tablet and capsule are also occurs pregastric absorption.
when water is not available. For these reason, tablets Due to reduction of dose; improve clinical
that can rapidly dissolve or disintegrate in the oral performance through a reduction of unwanted
cavity have attracted a great deal of attention effects.
(Seager 1998) The risk of chocking during oral
administration is avoided.
United States Food and drug administration (FDA)
defined fast dissolving tablet (FDT) as “a solid Have benefit when an ultra rapid onset of
dosage form containing medicinal substance or action required such as in motion sickness,
active ingredient which disintegrate rapidly usually allergic attack and in case of coughing.
within a matter of seconds when placed upon the Bioavailability can be increasd, particularly in
tongue.”European Pharmacopoeia described orally cases of hydrophobic drugs.
disintegrating tablets as “uncoated tablets intended Ability to provide advantage of liquid
to be placed in the mouth where they disperse medication in the form of solid preparation.
rapidly before being swallowed and as tablets which Due to stability for longer duration of time fast
should disintegrate within 3 min” (Yourong et al., dissolving tablets shows the advantage of solid
2004 and Bandari et al., 2008) dosage form in terms of stability and liquid
dosage form in terms of bioavailability.
Fast dissolving tablets are also define as mouth- 1.2 Selection of drugs:
dissolving tablets, melt-in mouth tablets, Oral
dispersible tablets, rapimelts, porous tablets, quick For the selection of drug, there are following criteria
dissolving tablet. (Arya et al., 2010):

1.1 Criteria for Fast dissolving Drug Delivery No bitter taste.

System: Dose lower than 20mg.
Small to moderate molecular weight.
The tablet should (Bhowmik et al., 2009):
Good stability in water and saliva.
Water is not required for swallowing. Partially unionized at the oral cavities pH.
Be compatible with taste masking. Oral mucosal tissue can be permeated.
Have a good mouth feel. 2. ENHANCEMENT OF SOLUBILITY
After administration of drug have either Solubility’ is defined as maximum amount of solute
minimum or no residue in mouth. that can be dissolved in a given amount of solvent to
Have Low sensitivity for environmental form a homogenous system at a specific
condition such as temperature and humidity. temperature. The solubility of a drug is represented
Allow the manufacture of the tablet using through various concentration expressions such as
conventional processing and packaging parts, percentage, molarity, molality , volume
equipments at low cost. fraction, mole fraction. The Indian Pharmacopoeia
1.2 Advantage of Fast Dissolving Drug Delivery defines solubility in terms of number of millilitres of
System: solvent required to dissolve 1g of solute.
Ease of administration in swallowing.

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The Biopharmaceutics Classification System 2.7 Adsorption technology

(BCS) is a scientific framework for classifying a 2.8 Ultra-rapid Freezing technology
drug substance based on its aqueous solubility and 2.9 pH adjustment technology
intestinal permeability and dissolution rate. These 2.10 Salt formation technology
factors govern the rate and extent of oral drug 2.11 Prodrug technology
absorption from immediate release solid oral-dosage 2.12 Nano-based technology
forms. It classifies drugs into four classes. Which 2.13 Other techniques:
are shows into the table 1: Co-solvency
Co-crystallization
Table 1: Biopharmaceutical classification system
Hydrotrophy
Low High Functional polymer technology
Permeability High I II Porous-microparticle technology
Low III IV Co-administration with other drugs
2.1 Particle size reduction technology: Particle
Solubility size is the first choice technique for the
enhancement of solubility. As the size reduces,
surface area volume ratio increases. Due to large
Model list of Essential Medicines of the World surface area of drug molecule, it allows a greater
Health Organization (WHO) has assigned BCS interaction with the solvent which ultimately cause
(Biopharmaceutics Classification System) increase in solubility (Lindenberg et al., 2004). This
classification on the basis of data available in the
technique has the various methods which are as
public domain. Out of 130 orally administered drugs
follows:
on the WHO list, 61drugs could be classified with
certainty (chavda et al., 2010). 2.1.1 Micronization: It is a conventional technique.
Due to decrease in particle size, dissolution rate of
84% of these drugs belong to class I drugs is increased by increasing the surface area but
17% of these drugs belong to class II it does not increase equilibrium solubility (Dubey.,
39% of these drugs belong to class III 2006) Micronization of drugs is done by milling
10% of these drugs belong to class IV technique using jet mill, rotor stator colloid mills
The rate and extent of absorption of class II & class etc. This process is not suitable for drugs having a
IV compounds is highly dependent on the high dose number because it does not change the
bioavailability which ultimately depends on saturation solubility of the drug (Blagden., 2007)
solubility (Lindenberg et al., 2004)
2.1.2 Nanonization: Drug solubility and
2.1 Techniques for Solubility Enhancement pharmacokinetics can be improved, while systemic
side-effects are decreased in nanonization process.
There are following techniques (Kumar et al.,
Wet milling, homogenization, emulsification,
2013):
solvent evaporation technique, Pearl milling, spray
2.1 Particle size reduction technology drying etc are the different techniques which are
2.2 Polymorphism technology used for the nanonization process. (Kumar et al.,
2.3 Drug dispersion technology 2013)
2.4 Emulsification technology
2.1.3 Sonocrystalisation: Sonocrystalisation is the
2.5 Liquid–Solid technology
novel approach for particle size reduction on the
2.6 Complexation technology
basis of crystallization by using ultrasound. It

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enhances solubility and dissolution of hydrophobic Mayersohnand Gibaldi. Once the solid dispersion is
drugs and also used to study its effect on crystal exposed to aqueous media and the carrier dissolve,
properties of drug. Recrystallization of poorly the drug is released as very fine to colloidal
soluble materials using liquid solvents and particles. Because of greatly enhanced surface area,
antisolvents has also been employed successfully to the dissolution rate and the bioavailability of poorly
reduce particle size (Sharma et al., 2007) water-soluble drugs are high. A water soluble carrier
results in a fast release of the drug from the matrix,
2.1.4 Supercritical fluid process: Supercritical and a poorly soluble or insoluble carrier leads to a
fluid (SCF) is novel nanosizing and solubilizing slower release of the drug from the matrix (Chiou et
technology. This process is also defined as a dense al., 1971)
non-condensable fluid. The flexibility and precision
offered by SCF processes allows micronization of Various pharmaceutical approaches are applied for
drug particles, often to sub-micron levels. Current the preparation of solid dispersions, include fusion
SCF processes have demonstrated the ability to method, solvent method, melting solvent method,
create nanosuspensions of particles 5-2,000nm in melt agglomeration process, solvent evaporation
diameter (Vemula et al., 2010) method, lyophilization method, mass extrusion
method, spray drying method and electro-spinning
2.2 Polymorphism Technology: Polymorphism is method etc.
the phenomenone for most of drugs which are exist
in more than one crystalline form. These different 2.3.2 Eutectic mixtures: A simple eutectic mixture
polymorphs of a drug are chemically similar, but consists of two compounds which are completely
they exhibit different physical properties which play miscible in the liquid state but only to a very limited
an important role in absorption and ultimately in extent in the solid state. Solid eutectic mixtures are
therapeutic effect. Amorphous form of drug is usually prepared by rapid cooling of two compounds
always more suited than crystalline form because of to obtain a physical mixture of very fine crystals
their higher energy, improved surface area and thus (Sharma et al., 2009) The concept of eutectic
the higher solubility. They require less energy to mixtures was originally proposed by Sekiguchi and
transfer a molecule into solvent because of greater Obi in 1960s (Sekiguchi et al., 1961) The resulting
aqueous solubility than crystalline form. So order of mixture has large surface area, more dissolution rate
dissolution of different solid forms of a drug is as and improved bioavailability.
follows (Bindu et al., 2010)
2.3.3 Solid solutions: Solid solution is a binary
Amorphous > Metastable polymorph > Stable system having solid solute dispersed in a solid
polymorph. solvent. Since the two compartments crystallize
together in a homogeneous one phase system, solid
2.3 Drug dispersion Technology: solutions are also called as molecular dispersion or
2.3.1 Solid dispersions: The term solid dispersion mixed crystals. In solid solution, the particle size is
refers to a group of solid products consisting of at reduced to molecular level. Solid solutions can be
least two different components, generally a classified into two categories:
hydrophilic matrix and a hydrophobic drug. The • Continuous solid solutions.
matrix can be either crystalline or amorphous. The • Discontinuous solid solution.
drug can be dispersed molecularly, in amorphous 2.4 Emulsification Technology: Emulsification
particles (clusters) or in crystalline particles (kumar technology is based on use of surfactant molecules
et al., 2009). The solid dispersions may also be for their stabilization purpose. The presence of
called solid-state dispersions, as first used by

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surfactants may lower the surface tension and bioavailability(Houssieny et al., 2010 and Khaled et
increase the solubility of the drug. al., 2001 )

2.4.1 Microemulsions: The term microemulsion 2.6 Complexation Technology:

was first used by Shulman in 1959. A
microemulsion is defined as a four component 2.6.1 Physical Mixture: Active drug with suitable
polymer in different ratios mixed in a mortar for
system which is composed of external phase,
about one hour with constant trituration. The
internal phase, surfactant and co-surfactant. Dilution
prepared mixture is passed through the sieve and
of microemulsions below the critical micelle
stored in dessicator over fused calcium chloride.
concentration of the surfactants could cause
precipitation of the drug however; the fine particle 2.6.2 Kneading method: Active drug with suitable
size of the resulting precipitate would still enhance polymer in different ratios is added to the mortar
absorption (Lawrence et al., 2000). Concentration of and triturated with small quantity of ethanol to
surfactant should be above the critical micelle prepare a slurry. Drug is mixed into the slurry with
concentration for the enhancement of solubility. constant trituration. The prepared slurry is then air
2.4.2 Micelles: A micelle is an aggregate of dried at 25oC for 24hrs. The resultant product is
pulverized and passed through the sieve and stored
surfactant molecules dispersed in a liquid colloid.
Surfactants can lower surface tension and improve in desiccators over fused calcium chloride (Das et
the dissolution of lipophilic drugs in aqueous al., 2012).
medium. They can also be used to stabilize drug 2.6.3 Co-precipitate method: Active drug is
suspensions. When the concentration of surfactants dissolved in ethanol at room temperature and
exceeds their critical micelle concentration, and the suitable polymer is dissolved in distilled water.
temperature of the system is greater than the critical Active drug and suitable polymers are mixed in to
micelle temperature or Kraft temperature, then the different molar ratios. The mixture is stirred at
formation of micelle occurs, entrapping the drugs room temperature for one hour and the solvent is
within the micelles (Dutt et al., 2003). This process evaporated. The resultant mass is pulverized and
is known as micellization and generally results in passed through sieve no. 80 and stored in a
enhanced solubility of poorly soluble drugs. desiccators (Shah et al., 2012).
2.5 Liquisoild Technology: Liquisoild technique is 2.7 Adsorption Technology: In this method the
a novel concept for oral drug delivery of drugs. This incorporation of the drug into hydrophilic carriers or
approach is suitable for immediate or sustain release drug solution deposition onto the adsorbents. The
formulations. The technique is based upon surface area of a drug available for contact with the
dissolving the insoluble drug in the suitable dissolution medium is increased by the use of
nonvolatile solvent, blending the liquid medicament particulate adsorbent carriers, whereby the drug is
with mixture of carrier and coating material, liquid bound to the carrier and thus cannot agglomerate.
medicament can be converted into non adhere, dry This is done by dissolving the drug in an organic
looking powder with acceptable flow properties and solvent and adsorbing this solution onto the carrier.
compression behaviour using by direct compression The evaporation of organic solvent results in a rapid
method. Drug release increases due to increase in precipitation of drug either on the surface or within
surface area. This improved drug release may result the pores of adsorbent material (Heike et al., 2006).
in a higher drug absorption in the gastrointestinal
tract and thus, an improved oral 2.8 Ultra-rapid Freezing Technology: This is a
novel, cryogenic technology that is used to reduce

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the particle size of poorly water soluble drugs and dissolution rates. This may be attributed to the
form stable formulation that are readily wetted and higher dissolution rate of a salt to its higher
have high dissolution rates. In this technology, drug solubility (relative to the free acid form) in the
is dissolved in a water miscible or anhydrous aqueous diffusion layer surrounding the solid.
solvent along with a stabilizer which acts as a Generally, an alkaloidal base is slightly soluble in
crystal growth inhibitor. Thereafter, drug/stabilizer water, but if the pH of medium is reduced by
solution is applied to a cryogenic liquid for ultra- addition of acid, the solubility of the base is
rapid freezing of the drug solution. Liquid nitrogen increased as the pH continues to be reduced. The
has been employed as a cryogenic liquid ( 1960 C). solubility of slightly soluble acid increases as the pH
The suspended frozen droplets can then be separated is increased by addition of alkali, the reason being
from the cryogen by allowing it to evaporate. The that a salt is formed (Kumar et al., 2013)
frozen particles are lyophilized to obtain highly
porous, dry and free-flowing micronized powders 2.11 Prodrug Formation Technology: Prodrug
(Evans et al., 2006) technology is applied to increase the chemical or
metabolic stability, higher water solubility or higher
2.9 pH Adjustment Technology: The absorption of solubility in lipid membranes, improved oral or
drug is largely dependent upon diffusion, which local absorption, enhanced brain penetration,
varies with pH of the individual regions within the reduced toxicity, and reduction of local irritation.
gastrointestinal tract, the pKa of the drug and
permeability, which are not only moderated by the 2.12 Nano-based Technology: Nanotechnology has
surface area of the region in which it is released, but emerged as a tremendous field in the medicine.
Nanotechnology refers broadly to the study and use
also the regional pH effects upon drug ionization.
of materials and structures at the nanoscale level i.e
pH adjustment can be used for both oral and
approximately 100 nm or less (Keck et al., 2006).
parenteral administration (Jain et al., 2004 ).
Nano-based formulations can be produced by two
Solubilised excipients that increase environmental
methods:
pH within a dosage form (tablet or capsule), to a
range higher than pKa of weakly-acidic drugs Bottom up techniques (precipitation
increases the solubility of that drug, and those methods)
excipients which act as alkalising agents may Top down techniques (size reduction by
increase the solubility of weakly basic drugs milling or high pressure homogenization).
(Graham et al., 1986). After pH adjustment, 2.13 Other Techniques:
ionisable compounds are stable and soluble. It can
also be applied to crystalline as well as lipophilic 2.13.1 Use of co-solvent: The solubility of a poorly
poorly soluble compounds (Tsi et al., 2008, Vila et water soluble drug can be increased frequently by
al., 2004 and Urrusuno et al., 1999 ). the addition of a water miscible solvent in which the
drug has good solubility known as co-solvents
2.10 Salt Formation Technology: Salt formation is (Strickley et al., 2004). Co-solvents are mixtures of
the most common and effective method of water and one or more water miscible solvents used
increasing solubility and dissolution rates of acidic to create a solution with enhanced solubility for
and basic drugs. It can lead to changes in solubility poorly soluble compounds (Vemula et al., 2010).
and permeability of the parent molecule, which can This technique is simple to produce and evaluate.
lead to improved bioavailability. Salts of acidic and
basic drugs have, in general, higher solubilities than 2.13.2 Co-crystallization: This approach is also
their corresponding acid or base forms. The use of referred as molecular complexes. A co-crystal may
salt forms is a well-known technique to enhance be defined as a crystalline material that consists of

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International Journal of Progressive Pharmacy Vol. 1 Isuue 1

two or more molecular (and electrically neutral) as HDDSTM (Hydrophobic Drug Delivery System).
species held together by non-covalent forces These drug particles provide large surface area for
(Almarsson et al., 2004). Co-crystals are alternative increased dissolution rate.
option to salt formation, for neutral compounds to
modify the chemical and/or physical properties of a 2.13.6 Co-administration with another drug:
drug without making or breaking covalent bonds. Combining of two or more drugs has an effect on
the improvement in the solubility as well as
Co-crystals are prepared by evaporation of a
synergetic therapeutic effect.
heteromeric solution or by grinding the components
together. 3. METHODS OF PREPERATION OF
2.13.3 Hydrotrophy: Hydrotrophy is a molecular FAST DISSOLVING TABLET:
phenomenon. Hydrotropy is defining as the For the preparation of fast dissolving tablet
enhancement in the solubility of insoluble or slightly there are two types of technologies are included:
soluble drugs in water by the addition of additives.
Hydrotrophes are a class of amphiphilic molecules Heating technology
that cannot form well organized structures, such as Non-heating technology
micelles, in water but do increase the aqueous 3.1 Heating technology
solubility of organic molecules. Along with
3.1.1 Cotton candy process: This process is also
solubilisation hydrotrophs serve many functions.
known as the “candy floss” process and forms the
The mechanism by which it increases solubility is
basis of Flash Dose technology (Kumar et al.,
more closely associated to complexation involving a
2013). The Flash dose technology is a fast
weak interaction between the hydrotrophic agents
dissolving drug delievery system, manufactured
and the solute. Solute consists of alkali metal salts
using Shearform technology in association with
of various organic acids (Vemula et al., 2010). They
Ceform technology to eliminate the bitter taste of
are known to exhibit influences on surfactant
the medicament (Myers et al., 1995 and Cherukuri
aggregation leading to micelle formation, phase
et al., 1995). The shearform technology uses a
manifestation of multicomponent systems with
unique spinning mechanism to produce floss like
reference to nanodispersion and conductance
crystalline structure, much like cotton candy. This
percolation, clouding of surfactants and polymers,
process involves the formation of matrix of
etc (Bindu et al., 2010)
polysaccharides by simultaneous action of flash
2.13.4 Functional polymer technology: Functional melting and spinning. This candy floss matrix is
polymer enhances the dissolution rate of poorly then milled and blended with active ingredients and
soluble drugs by avoiding the lattice energy of the excipients after re-crystallization and subsequently
drug crystal, which is the main barrier to rapid compressed to FDT (Siddiqui et al., 2010). This
dissolution in aqueous media. This can also be process is applicable only for thermostable
applied to heat sensitive materials and oils. compound.

2.13.5 Porous microparticles technology: In this Characteristics: It can accommodate high doses of
technology, the poorly water soluble drug is drug and offers improved mechanical strength. The
entrapped in a microparticle having a porous, water tablets manufactured by this process are highly
soluble, sponge-like matrix. When mixed with porous in nature and offer very pleasant mouth feel
water, the matrix dissolves, wetting the drug and due to fast solubilization of sugars in presence of
leaving a suspension of rapidly dissolving drug saliva (Gupta et al., 2010).
particles. This is the core technology which is called

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International Journal of Progressive Pharmacy Vol. 1 Isuue 1

3.1.2 Tablet molding process: It is of two types: extrude which are finally cut into even segments
using heated blade to form tablets (Bhaskaran et al.,
3.1.2.1 Solvent method: This process is also known 2002, Yu et al., 2008).
as compression molding. The major components for
this process are water-soluble ingredients (Yourong Characteristics: The dried product can be used to
et al., 2004). This process involves the moistening coat granules of bitter tasting drugs and thereby
the powder blend with a hydro alcoholic solvent mask their bitter taste.
followed by compression at low pressures in molded
3.1.4 Sublimation: In this process substance
plates to form a wetted mass. The solvent is then
directly gets converted to the gas phase without
removed by air-drying. The tablets manufactured in
passing through an intermediate liquid phase. It
this manner are less compact than compressed
involves formation of a porous matrix, by
tablets and posses a porous structure that hastens
dissolution (Kumar et al., 2013). Because moulded incorporating volatile ingredients in the formulation
tablets are usually compressed at a low pressure that is later subjected to a process of sublimation
than are conventional compressed tablets, a higher (Kumar et al., 2013). The presence of a highly
porous structure in the tablet Matrix is the key factor
porous structure is created to enhance the
for rapid disintegration of FDTs. Even though the
dissolution. To improve the dissolution rate, the
conventional tablets contain highly water-soluble
powder blend usually has to be passed through a
ingredients, they often fail to disintegrate rapidly
very fine screen.
because of low porosity. To improve the porosity,
3.1.2.2 Heat molding: This process involves volatile substances such as camphor can be used in
preparation of a suspension that contains a drug, tableting process, which sublimated from the formed
agar and sugar (e.g. mannitol or lactose) and tablet (Koizumi et al., 1997). Highly volatile
pouring the suspension in the blister packaging ingredients like ammonium bicarbonate, ammonium
wells, solidifying the agar at the room temperature carbonate, benzoic acid, menthol, camphor,
to form a jelly and drying at 30 C under vacuum naphthalene, urea, urethane or phthalic anhydride
(Bhowmik et al., 2013). The mechanical strength of could be compressed along with other excipients
moulded tablets is a matter of great concern. into a tablet (Kumar et al., 2013).
Binding agents, which increase the mechanical
Characteristics: Porous structure that enhances
strength of the tablets, need to be incorporated
dissolution by using volatile material or solvent e.g.
(Kumar et al., 2013). Another process used is called
cyclohexane, benzene etc. Disintegration time for
no vacuum lyophilization, which involves the
these types of tablets is 10-20secs.
evaporation of a solvent from a drug solution or
suspension at standard pressure (Gupta et al., 2010). 3.1.5 Granulation method:
Characteristics: Molded tablets are very less 3.1.5.1 Wet granulation method: Bonadeo et al.
compact than compressed tablet porous structure described the process of producing wet granulation
that enhances disintegration/dissolution and finally in a fluidized bed (Bonadeo et al., 1998). They
absorption increased. found that the tablet disintegrate within 3 to 30
seconds in to saliva due to the acid component of
3.1.3 Mass extrusion: This technology involves
the effervescent agent. This is because the tablet
softening of the active blend using the solvent
disintegrates by surface erosion and is not amenable
mixture of water soluble polyethylene glycol and
to rapid dispersion or disintegration in water prior to
methanol and expulsion of softened mass through
oral administration to swallowing- compromised
the extruder or syringe to get a cylindrical shaped
patients. The mixture for wet granulated is prepared

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International Journal of Progressive Pharmacy Vol. 1 Isuue 1

with an aqueous solution of a water-soluble or into the wells of the preformed blister packs. The
water-dispersible polymer (e.g., polyethylene trays holding the blister packs are passed through
glycols), carrageenan, and ethylcellulose), which liquid nitrogen freezing tunnel to freeze the drug
consisted of 1–10% of the final weight of the solution. Then the frozen blister packs are placed in
granule in a fluid bed. Granules with high porosity refrigerated cabinets to continue the freeze drying
and low apparent density were obtained and then and packaged.
granules were made into tablets.
Characteristics: The preparations are highly
Characteristics: Due to porus structure of tablet porous, have high specific surface area, dissolve
complete disintegrate with in the 3 minutes. rapidly and ultimately show improved absorption
and bioavailability.
3.1.5.2 Dry granulation: Eoga and Valia described
the method of dry granulation (Eoga et al., 1999). 3.2.2 Direct compression: It is the easiest way for
Higher density alkali earth metal salts and water- the manufacturing of tablets. This technique can
soluble carbohydrates usually do not provide quick now be applied to preparation of FDT because of the
disintegration and a smooth mouth feel. Low- availability of improved excipients especially
density alkali earth metal salts and water soluble superdisintegrants (crosscarmelose, microcrystalline
carbohydrates are also difficult to compress and cellulose etc.) and sugar based excipients (dextrose,
caused inadequate content uniformity. For these maltose, lactose etc.). This process has the limited
reasons, low-density alkali earth metal salts or number of steps.
water-soluble carbohydrates are pre-compacted, and
then resulting granules are compressed into tablets Characteristics: It is most cost effective tablet
that dissolve fast. In this process, required density manufacturing technique.
for the powder material is of 0.2–0.55 g/mL. 3.2.3 Spray drying: This technology produces
3.1.5.3 Phase-transition process: Prepared by highly porous and fine powders as the processing
compressing a powder containing two sugar solvent is evaporated during the process (Allen et
alcohols with high and low melting points and al., 2001). In this process hydrolyzed or non-
subsequent heating at a temperature between their hydrolyzed gelatine used as a supporting material
melting points. The tablet hardness was increased and mannitol as a bulking agent and crosscarmellose
after heating process due to increase of inter particle as disintegrating agent and an acidic or alkali
bond induced by phase transition of lower melting materials are used to enhance the dissolution or
point sugar alcohol (Kuno et al., 2005). disintegration.

Characteristics: The compatibility increased and so Characteristics: Prepared tablet disintegrates

sufficient hardness gained by the formulation. within 20 seconds when immersed in an aqueous
medium.
3.2 Non-heating process:
3.2.4 Nanonization: A recently developed
3.2.1 Lyophillization or Freeze drying: Nanomelt technology involves reduction in the
Lyophilization is a pharmaceutical technology particle size of drug to nanosize by milling the drug
which allows drying of heat sensitive drugs and using a proprietary wet-milling technique. This
biologicals at low temperature under conditions that process involves the size reduction of drug to
allow removal of water by sublimation (Nail et al., nanosize by milling the drug using a proprietary
2005). The drug is dissolved or dispersed in an wet-milling technique. The nanocrystals of the drug
aqueous solution of a carrier. The mixture is poured are stabilized against agglomeration by surface

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International Journal of Progressive Pharmacy Vol. 1 Isuue 1

adsorption on selected stabilizers, which are then 4.2 Flavours: Peppermint flavour, cooling flavor,
incorporated into FDTs. flavor oils and flavoring aromatic oil, peppermint
oil, clove oil, bay oil, anise oil, eucalyptos oil thyme
Characteristics: It is used for poorly water soluble oil, oil of bitter almonds. Flavoring agnets are also
drugs. It leads to higher bioavailability and included such as vanilla, citus oils, fruit essences
reduction in dose, cost effective manufacturing etc.
process, conventional packaging due to exceptional
durability and wide range of doses (up to 200 mg of 4.3 Sweetners: Aspartame, Sugars derivatives
drug per unit).
4.4 Fillers: Directly compressible spray dried
3.2.5 Compaction: Mannitol, Sorbitol, xylitol, calcium carbonate,
magnesium carbonate, calcium phosphate,
3.2.5.1 Melt granulation: Prepared by calcium sulfate, pregelatinized starch,
incorporating a hydrophilic waxy binder (super magnesium trisilicate, aluminium hydroxide.
polystate) PEG-6-stearate. Super polystate not only
acts as binder and increase physical resistance of 4.5 Surface active agents: sodiumdoecylsulfate,
tablet but also helps the disintegration of tablet. sodiumlaurylsulfate, polyoxyethylene sorbitan
fatty acid esters (Tweens), sorbitan fatty acid
Characteristics: It melts in the mouth and esters (Spans), polyoxyethylene stearates.
solubilizes rapidly leaving no residue.
4.6 Lubircants: Stearic acid, Magnesium stearate,
3.2.6 Three-dimensional Printing (3DP): Three- Zinc state, calcium state, talc, polyethylene
dimensional printing (3DP) is a rapid prototyping glycol, liquid paraffin, magnesium laury sulfate,
(RP) technology. Prototyping involves constructing colloidal silicon dioxide.
specific layers that uses powder processing and
liquid binding materials. A novel fast dissolving 5. Characterization of fast dissolving tablet:
drug delivery device (DDD) with loose powders in
it was fabricated using the three dimensional 5.1 Drug excipient compatibility test:
printing (3DP) process. Based on computer-aided Detection of any changes in chemical
design models, the DDD containing the drug constituent of the drug when combined with the
acetaminophen were prepared automatically by 3DP other excipient is determined. This test can be
system (Yu et al., 2008). It was found that rapidly performed by differential scanning calorimeter and
disintegrating oral tablets with proper hardness can fourier transform infrared spectroscopy.
be prepared using TAG. The rapid disintegration of
the TAG tablets seemed due to the rapid water 5.2 Pre-compression evaluation (Lachmann et al.,
penetration into the tablet resulting from the large 1998):
pore size and large overall pore volume (Ito et al.,
5.2.1 Bulk density: Weigh the 10 g of powder
1996).
(presieved 40-mesh) and poured into the 100ml
4. Excipients measuring cylinder and note volume occupied by
the powder via a large funnel. It is expressed in g/ml
4.1 Super disintegrants: Crosspovidone, and is given by,
Microcrystalline cellulose, sodium starch
glycollate, sodium carboxy methyl cellulose, Db = M/ Vb
pregelatinzed starch, calcium carboxy methyl
Where, M is the mass of powder
cellulose, and modified corn starch.
Vb is the bulk volume of the powder.

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International Journal of Progressive Pharmacy Vol. 1 Isuue 1

5.2.2 Tapped density: Weigh the 10 g of powder 3 18 – 21 Fair Passable

(presieved 40-mesh) and poured into the 100ml
measuring cylinder and note volume occupied by 4 23 – 35 Poor
the powder via a large funnel or in mechanical 33 – 38 Very Poor
5
tapper apparatus, which is operated for a fixed
number of taps (~1000 times) until the powder bed 6 < 40 Very Very Poor
volume has reached a minimum. It is expressed in
g/ml and is given by,
5.2.5 Hausner ratio: Hausner ratio is an indirect
Dt = M / Vt
index of ease of powder flow. It is calculated by the
Where, M is the mass of powder following formula.
Vt is the tapped volume of the powder.
5.2.3 Angle of repose: The powder mixture was Hausner ratio = Dt/ Db
allowed to flow through the funnel fixed to a stand Where, Dt is the tapped density.
at definite height (h). The angle of repose was then Db is the bulk density.
calculated by measuring the height and radius of the Lower Hausner ratio (<1.25) indicates better flow
heap of powder formed. Care was taken to see that properties than higher ones (>1.25).
the powder particals slip and roll over each other
through the sides of the funnel. Relationship 5.3 Evaluation of fast dissolving tablet:
between angle of repose and powder flow property.
5.3.1 General appearance: The general
tan ( q ) = h / r appearance of a tablet is its visual identity and
overall elegance including size and shape, tablet
q = tan-1 (h / r)
thickness and unique identification marking.
Where, q is the angle of repose.
h is the height in cm 5.3.2 Uniformity of weight: Take twenty tablets
r is the radius in cm. and their weight was determined individually and
Table 2: Angle of Repose as an Indication of collectively on a digital weighing balance. The
Powder Flow Properties average weight of one tablet was determined from
Sr. No. Angle of Repose (°) Type of Flow the collective weight. The weight variation test
1 < 20 Excellent would be a satisfactory method of determining the
2 20 – 30 Good drug content.
3 30 – 34 Passable Table 4: Weight Variation Specification as per IP
4 > 34 Very Poor
Sr. No. Average Weight Maximum %
5.2.4 Carr’s index (or) % compressibility:
of Tablet difference allowed
Table 3: Relationship between % compressibility
and flowability 1 130 or less 10

Sr. No. % Compressibility Flow ability 2 130-324 7.5

1 5 – 12 Excellent
3 More than 324 5
2 12 – 16 Good

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International Journal of Progressive Pharmacy Vol. 1 Isuue 1

5.3.3 Hardness: It is also termed as tablet room temperature for 2 weeks. Required humidity
crushing strength. The limit of hardness for the will be achieved by keeping saturated calcium
FDT is usually kept in a lower range to facilitate chloride solution at the bottom of the desecrator for
early disintegration in the mouth. The hardness of 3 days. One tablet as control (without super
the tablet may be measured using conventional disintegrant) will be keep to check the moisture
hardness testers (Monsanto tablet hardness tester, uptake by the other excipients. Tablets will be
Pfizer hardness tester). It is expressed in kg or weighed and the percentage increase in the weight
pound (Lachmann et al., 1998). will be recorded.

5.3.4 Friability: Tablet friability is measured by 5.3.7 In-vitro dissolution studies: Release of drug
ROCHE friabilator (USP). A pre weighed tablet from bilayer matrix tablet will be determined by
sample is placed in the friabilator. Friabilator USP Paddle method. The dissolution rate will be
consist of a plastic-chamber that revolves at 25 studied using 900 ml appropriate dissolution
rpm, dropping those tablets at a distance of 6 inches medium. 0.1N HCl, pH 4.5 and pH 6.8 buffers
with each revolution. The tablets were rotated in should be used for evaluation of fast dissolving
the friabilator for at least 4 minutes. At the end of tablet. (paddle speed of 25-75 rpm is commonly
test tablets were dusted and reweighed at 25 rpm used.
for 4 min. and calculated by the following formula:
5.3.8 Modified disintegration test: A 10cm
Percentage friability= [initial weight-final petridish is filled with 10 ml of water. The tablet is
weight)/initial weight] ×100 carefully put in the center of petridish and the time
for the tablet to completely disintegrate into fine
5.3.5 Wetting time and water absorption ratio: particles will be noted.
Wetting time of dosage form is related to with the
contact angle. Lower wetting time implies a quicker 5.3.9 In-vitro dispersion time: Tablet will be
disintegration of the tablet. The disintegration time added to 10 ml of phosphate buffer solution, pH 6.8
for FDT needs to be modified as disintegration is at 37±0.5°c. Time required for complete dispersion
required without water, thus the test should mimic of a tablet will be measured.
disintegration in salivary contents. For this purpose,
a petridish (10 cm diameter) was filled with 10 ml 5.3.10 Drug content uniformity: Drug content of
of water. The tablet was carefully placed in the fast dissolving tablets will be calculated by
center of petridish and the time for the tablet to weighing ten tablets of each formulation,
completely disintegrate into fine particles was noted. pulverizing to a fine powder. A quantity of powder
The water absorption ratio, R can be the determined equivalent to 10 mg of drug dissolved in methanol
according to the following equation; and solution will be filtered through a 0.45 m
whatmann filter paper. Drug content will be
R = 100 (Wa-Wb) / Wb determined by measuring the absorbance UV visible
spectrophotometer after appropriate dilution with
Wb; weight of the tablet before keeping in the
methanol. The drug content will be determined
petridish
using calibration curve. The mean percent drug
Wa; wetted tablet from the petridish is taken and
content will be calculated as an average of three
reweighed (Morita et al., 2002) .
dimensions.
5.3.6 Moisture uptake study: Ten tablets from
each formulation will be kept in desiccators over
calcium chloride at 37ºC for 24h. The tablets will be
weighed and exposed to 75% relative humidity, at

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