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_________________________________________Review Article
Taste Masking Technologies: An Overview and Recent
Updates
Vishnumurthy Vummaneni* and Dheeraj Nagpal
Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Sector-125,
Noida, Uttar Pradesh, India.
__________________________________________________________________________________
ABSTRACT
Taste, smell and texture are the important factors in development of oral dosage forms. Taste is now a factor
influencing the patient compliance and product quality. “The worser the taste of the medication, the better
the cure” an older attitude which now totally changed. Taste masking of obnoxious drugs has gained the
importance as the most of them are administered orally. This reason is an initiative for the development of
various taste masking technologies by which the characteristics of the dosage form is improved and good
patient compliance is achieved. The main objective of this review is to explore various methodologies for
masking the taste of obnoxious drugs, applications, evaluation and also the recent trends in taste masking
technologies.
Key Words: Taste masking, Bitter, Patient compliance, Drug product, Dosage form.
INTRODUCTION
Taste is the ability to detect the flavour of
substances like food, drugs etc. Taste is now
became an important factor governing the patient
compliance. It gained importance as the most of the
drugs are administered through oral route.
Administration of unpalatable drugs is hampered
by their unpleasant taste particularly in case of
paediatric and geriatrics. Various methods like
coating, inclusion complexes, microencapsulation,
granulation, adsorption, prodrug approach, addition
of flavours and sweeteners, ion exchange resins are
used for masking the taste of obnoxious drugs.
However, there is no universal method for taste
masking. Each method offers specific advantages
and applications. One method is not suitable for
taste masking all the obnoxious drugs. Several
parameters like extent of bitter taste, dose, dosage
form and type of the patient influence the method
to be used for masking the taste of the bitter drugs.
Evaluation of taste masking by electronic tongue is
a recent innovation. Advatab, Microcaps, Liquitard,
Kleptose, Formulplex and Formulcoat are the new
taste masking technologies which are found to be
better than existing ODT technologies like Zydis,
Orasolv and Quicksolv etc. In addition to oral drug
delivery, the taste masked drug delivery research is
gaining importance for improving the quality of the
treatment for paediatrics and geriatrics.
TYPES AND MECHANISM OF TASTE
Taste is one of the traditional five senses and is the
ability to detect the flavour of substances such
as food, certain minerals, and poisons, etc. It
determines the selection of food, its palatability
and stimulation of reflexes for secretion of saliva,
gastric juices and pancreatic juices. The sensation
of taste can be categorized into1,3:
a) Sweet (sugars, glycerol)
b) Saltish (sodium)
c) Sour (acidic substances)
d) Bitter (quinine, nicotine)
e) Umami
Humans receive tastes through sensory
organs, taste buds, ( also known as gustatory
calyculi) concentrated on the upper surface of
the tongue.
Taste buds
Taste buds are the structures present primarily on
the surface of tongue which contains receptors that
mediate the sense of taste.
Distribution2
Taste buds are also present on palate, pharynx,
epiglottis and larynx. Tongue consists of numerous
structures called papillae. There exists different
types of papillae, of which fungiform papillae
contain single taste bud on the tip and
circumvallate papillae contains several taste buds.
However, filiform papillae donot contain taste buds
even their number is more. Different types of tastes
have different threshold concentration based on the
distribution of taste buds on surface of the tongue,
enlisted in table no:1
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Structure
Taste bud is oval in shape and opens into epithelial
surface through a small opening called taste pore(
Fig.no: 1). Microvilli protrudes from the taste pore
arising from the individual taste cells. Each taste
bud has 50-100 receptors and support cells. Based
on the electron microscopy, receptors are classified
into basal, dark, intermediate and light.
The receptors are connected through synapse ( ATP
releasing ) to sensory neuron, leading back to the
brain. The sensation of taste thus resides in the
brain. However, a single sensory neuron can be
connected to several taste cells1-3.
Interpretation of Taste
The receptor cells are of two types functionally.
One is ion channel type receptor( Fig. no: 2), is a
trans membrane protein which allows the ions that
give rise to sensation of salt and sour. These ionic
interactions causes electrical change within taste
cells that trigger neurons to send chemical signals
(that translate into neuro transmission) to the brain.
These cells have a net negative charge in normal
state. Tastants alter this state by using various
means to increase positive ion concentration with
in the taste cell. This depolarization causes the cell
to release neuro transmitters, there by relaying the
electrical messages to brain2,3.
The other is a surface protein receptor, allows
binding of tastants ( molecules having sense of
taste ) which give the sensation of sweet, bitter and
umami. In case of bitter taste, stimuli acts by
binding to G-Protein coupled receptors( Fig. no: 3).
Further leads to the splitting of G-Protein subunits
and activation of the nearby enzyme present, finally
resulting the release of secondary messengers. The
secondary messengers intiate the release of Ca+2
ions from endo plasmic reticulum of the taste cell.
The increased concentration of calcium ions in the
cell leads to depolarization and release of neuro
transmitters. This message is sent to the brain
through sensory neuron and interpreted as “bitter”
taste3,4.
TASTE MASKING TECHNIQUES
Various techniques reported in the literature are as
follows5-6,8-11
Addition of flavours and sweeteners
Coating
Microencapsulation
Ion exchange resin
Inclusion complexes
Granulation
Adsorption
Prodrug approach
Bitterness inhibitors
Multiple emulsion
Gel formation
Factors that are taken into consideration during
the taste-masking formulation include5-10
Extent of the bitter taste of the API
Required dose load
Drug particulate shape and size
distribution
Drug solubility and ionic characteristics
Required disintegration and dissolution
rate of the finished product
Desired bioavailability
Desired release profile
Required dosage form
Taste masking by coating5-8
Coating is one of the commonly used and efficient
method used in taste masking technologies. The
coating material is classified into lipids, polymers
and sugars. These materials can either be used
alone or in combinations, as a single layer or
multiple layer coat to achieve taste masking of the
bitter drugs as reported in table no:3.
Hydrophobic polymers have been popularly used
for coating of bitter drugs than hydrophilic
polymers to achieve taste masking. Sweeteners can
also be incorporated in the coating solution of
better taste masking.
Multilayer coating has been done to overcome the
coating imperfections otherwise leads to decrease
in taste masking performance, especially for
aggressively bitter drugs.
Of the several types of materials existing for
coating, polymers are widely used for coating.
Polymers are further classified into water soluble,
water insoluble and their mixtures (Fig. 4).
Examples of each type of polymer are listed in
table no:2.
Acidic compounds like citric acid and malic acid
are used for creating acidic micro environment to
promote the release of drug in the upper intestine
from the drug particles coated with reverse enteric
polymers6.
Water soluble organic acids and their salts such as
tartaric acid can be used with hydrophilic polymers
for achieving taste masking. These acids promote
salivation to facilitate the formation of thick,
viscous and a mouldable particle paste, which
increases the swallowing of that drug.
Multi layer coating with addition of first spacing
layer reduces the coating imperfections, drug
excipient incompatabilities there by improving the
taste masking efficiency.
Ion exchange resins
Ion exchange resins are synthetic organic polymers
inert in nature, consists of a hydrocarbon chain to
which insoluble groups are attached and they have
ability to exchange their labile ions for ions present
in the solution with which they are in contact.
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Types5,9,10
Based on the charge of the functional groups
present, ion exchange resins are classified into
cation exchange resins and anion exchange resins.
With in each category, they are classified into
strong and weak depending on their affinity for
counter ions.
Cation exchange resins are exchangers of sodium,
potassium or aluminium salts and anionic resins are
for chloride ions. The drugs are loaded on to the
resins by column method and batch method5,8-11.
Column method
Highly concentrated drug solution is passed
through the column containing resins. Maximum
efficiency is best obtained by the column method.
Batch method
In this method the drug solution is agitated with a
quantity of resin until equilibrium is attained.
Reactions involved in complexation of drug with
resins
Acidic drug
Re-N(CH3)+ 3 Cl- + Drug- Re-N(CH3)+ 3
Drug- + Cl-
Basic drug
Re-COO-H+ + Drug+ Re-COO- Drug+
+ H+
Typical reactions involved in gastrointenstinal
fluids
Acidic drug
In stomach
Re-N(CH3)+ 3 Drug- + HCl Re-
N(CH3) 3 Cl + Drug ( Free form)
In intestine
Re-N(CH3)+ 3 Drug- + NaCl Re-
N(CH3)+ 3 Cl- + Drug ( Sodium salt)
Basic drug
In stomach
Re-COO- Drug+ + HCl Re-COOH +
Drug- HCl
In intestine
Re-COO- Drug+ + NaCl Re-COONa
+ Drug-HCl
In taste masking by ion exchange resins, the resin-
drug complexes formed will elute only a limited %
of drug in the saliva PH. Thus the taste of the drug
is masked without interrupting the drug release
profile ( as shown in above reactions).
Table no: 4 is a literature report of various ion
exchange resins employed in taste masking of
drugs. Examples of drugs listed in table no: 5 are
those by which the taste of the drug is masked by
ion exchange resins.
Flavours and sweeteners
Sweeteners are commonly used in taste masking of
drugs. These are commonly used in combination
with other taste masking technologies. These can
be mixed with bitter drugs so as to improve the
taste of the core material. Sweeteners are classified
into natural and synthetic, based on the origin.
Synthetic sweeteners such as sucralose, aspartame,
saccharin are showing their prominence in taste
masking than the natural ones. These sweeteners
are used in combination with sugar alcohols like
lactitol, maltitol and sorbitol to decrease their after-
taste perception. Sucralose can be used with acids (
citric acid) to increase the taste masking efficiency
of the sweetener[11,12]. Each sweetener will have
their own significance in taste masking and
different value of sweetness when compared to
standard ( Sucrose), examples listed in table no:6.
There is often a correlation between the chemical
structure of a compound and its taste. Low
molecular weight salts tend to taste salty where
higher molecular weight salts tend toward
bitterness. Nitrogen containing compounds, such as
the alkaloids, tend to be quite bitter.
Flavours are also commonly used in taste masking
of drugs in solids and liquid dosage forms.
Flavours are classified into natural and artificial(
table no:7). Selection of suitable flavouring agent
to be added depends on the original sensation of
drug substance (table no:8). The cooling effect of
some flavours aids in reducing after-taste
perception. Eucalyptus oil is a major constituent of
many mouth washes and cough syrup formulations.
Examples of various classes of drugs of which the
taste masking is achieved by the use of sweeteners
and flavouring agents are listed in table no:9.
Formation of inclusion complexes
Inclusion complex is a ‘host-guest’ relationship in
which the host is complexing agent and guest is the
active moiety. The complexing agent is capable of
masking bitter taste either by decreasing its oral
solubility or decreasing the availability of drug to
taste buds. Vanderwaal forces are mainly involved
in inclusion complexes4-11.
β- cyclodextrin is widely used complexing for taste
masking of drugs due to its sweet taste and is non
toxic in nature.
Table no:10 is a literature report of various
complexing agents used for taste masking of bitter
drugs.
Prodrug approach
Prodrugs are therapeutic agents that are initially
inactive but on biotransformation liberate active
metabolite by which the therapeutic efficacy is
obtained.
Molecular geometry of the substrate is important
for the taste receptor adsorption reaction i.e.,
mechanism of taste. Hence if any alteration is done
in molecular geometry, it lowers the adsorption rate
constant. Thus taste masking can be achieved
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through prodrug approach. Other advantages of
prodrugs include change in aqueous solubility,
increase lipophilicity, improved absorption, less
side effects and change in membrane permeability
etc10,11. Table no: 11gives a list of active moieties
and their prodrug approaches done in recent years.
Microencapsulation
Microencapsulation is a process in which the active
moiety ( solid or liquid droplets) is coated with a
polymeric material or film.
Types of microencapsulation include5,6,11:
Air suspension coating
Coacervation phase separation
Spray drying
Spray congealing
Solvent evaporation
Pan coating
Interfacial polymerization etc.
Of these processes, first four are mostly used
techniques for achieving taste masking.
Microencapsulation by coacervation phase
separation consists of three steps carried out under
continuous agitation, such as: formation of three
immiscible phases, deposition of coating and
rigidization of coating.
Polymers and their selection selection of coating
polymer is an important factor to be considered for
taste masking by coating.
Ideal characteristics of a coating polymer
Should not allow the release of drug in
oral cavity, but should allow the release of the drug
at the expected site ( intestine or stomach).
Should be insoluble in salivary PH (6.8)
but Should be soluble in gastric
PH ( 1.2)
Choosing one of the polymers is not a simple
selection. Before making the decision on coating
material, the following factors of drug are to be
considered5,6,10,11
Particle size
Flow properties
Moisture sensitivity
Long term stability
Effect of temperature on processing
Form of Drug delivery etc.
Once the type of coating and polymer is decided,
then the level of coating has to be optimized. Thick
coating may cause problems both in terms of size
and cost. However, by coordinating the right type
of coating material it is possible to mask the bitter
taste of the drug completely while at the same time
not affecting the intended drug release. Table
no.:12 gives a literature report on various coating
materials used for taste masking the drugs.
Granulation
Taste masking of a bitter taste drug can be masked
by granulation process. Granulation is major and a
common process in tablet production. In this
approach, saliva insoluble polymers are used as
binding agents in the tablet preparation. As these
polymers are insoluble in saliva, thus the bitter
taste of the drug can be masked[6-8]. The taste
masked granules can also be formulated as
chewable tablet and rapidly disintegrating tablets.
Table no.13 gives the literature report on the list of
drugs whose taste is masked by granulation
techniques by using saliva insoluble polymers.
Adsorption
Adsorbate of bitter tasting drug can be considered
as less saliva soluble version of that drug. In this
technique, adsorbates of the bitter drugs are
prepared by adsorption process. This process
involves the adsorption of the drug solution using
insoluble materials like silica gel, bentonite ,
veegum etc. The adsorbate ( resultant powder) is
dried and used for the formulation of final dosage
forms10.
Taste suppressants and potentiators
Most of Linguagen’s bitter blockers ( adenosine
mono phosphate) compete with bitter substances to
bind with GPCR sites. In general, hydrophobic
nature of these bitter substances have good binding
affinity to the receptor sites. Lipoproteins are
universal bitter taste blockers. Neohesperidine
phospholipids have bitter taste suppression
characteristics by chemically interacting with the
taste receptors. Cooling and warming agents
suppress unpleasant taste of medicament by
subjecting taste receptors to extreme sensations to
overcome/ overpower the bitter taste so as to
confuse the brain. Eucalyptol ( Cooling agent) and
Methyl salicylate ( Warming agent) mixture was
used for suppression of the bitter taste of Thymol3,5-
7.
Potentiators increase the perception of the taste of
sweeteners and mask the unpleasant taste. Various
potentiators include thaumatine, neohesperidine
dihydro chalcone ( NHDC) and glycyrrhizin
increase the perception of sodium or calcium
saccharinates, saccharin, acesulfame, cyclamates
etc. Thaumatine along with sugar alcohols to
achieve taste masking of bromhexine[5,8].Table
no:14 enlists various taste suppressants and
potentiators used for taste masking.
Liposomes and multiple emulsions5,6
Liposomes are carrier molecules comprising
several layers of lipids, in which the bitter drug is
entrapped within the lipid molecule. Oils,
surfactants, polyalcohols and lipids effectively
increase the viscosity in the mouth due to which the
time of contact between the bitter drug and taste
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receptors is decreases, thus improving the overall
taste masking efficiency.
Inhibition of bitterness of drugs by phospholipids
such as phosphatidic acid, phosphatidylinositol,
soya lecithin etc has been reported. The bitterness
of Chloroquine phosphate in HEPES buffer ( PH
7.2) is masked by incorporating into a liposomal
formulation prepared with egg phosphatidyl
choline.
Multiple emulsions is also a good approach for
taste masking of bitter drugs. This is achieved by
dissolving the drug moiety in the inner aqueous
phase of w/o/w emulsion with good self life
stability. o/w/o emulsion is a type of multiple
emulsion in which water globules themselves
containing dispersed oil globules, conversely w/o/w
emulsions are those in which internal and external
aqueous phases are separated by the oil. Both types
of multiple emulsions are prepared for Chloroquine
sulphate and reported to be partially effective in
masking the bitterness of the drug. Examples of
drug listed in table no: 15 indicates the use of
liposomes and multiple emulsions technique in
taste masking.
EVALUATION OF TASTE MASKING
EFFECT
All the medicines are not always compatible. So,
there is a necessity of incorporating an agent for
taste masking of the drug and provides the patient
with a pleasant product experience. Next step is to
determine what additional functional excipients are
required for the final product. These excipients
include sweeteners, flavours and super
disintegrants. Before incorporation of these
materials all the preformultion parameters have to
satisfy and they should be physically, chemically
and therapeutically compatible with the drug and
should be optimized.
The evaluation is classified into two types[8,10,11].
They are Subjective methods and Objective
methods( table no: 16).
Evaluation of solid and liquid dosage forms (
except microspheres)
Soutakagi., et al. discovered a multi channel taste
sensor ( E- tongue) which is almost similar to the
human tongue. This sensor consists of transducer,
which is composed of several kinds of polymer/
lipid membrane with different characteristics. Taste
information is transformed into electrical signals of
membrane potential of the receptor. It was
previously reported to record the bitterness of
quinine and acesulfame K, as a bitterness
inhibitor[10,11].
E-tongue provides a fast and simple assessment of
oral formulations like chewable tablets, liquids,
rapid dissolving tablets, films and lozenges etc.
Evaluation of microspheres
This can be done by determining the rate of release
of the drug from microspheres. The reason is that
the drug release rate can serve as an index of the
degree of taste masking achieved.
Recent innovations
Taste analyzing system by Alpha MOS is now
commercially available. It consists of a taste sensor
comprised of silicon transistors with an inorganic
coating that governs the sensitivity and selectivity
of each individual sensor. The life of the sensor
lasts for about 1 year.
RECENT TRENDS13,14,15
AdvaTab ODT Technology
Advatab ODT Technology is developed by
APTALIS Pharmaceutical technologies. Various
advantages offered by this technology includes
high physical stability, stability during package and
transport, pleasant taste ( with Microcaps
technology) and good patient compliance.
Microcaps ODT Technology
Microcaps ODT technology is developed by
APTALIS Pharmaceutical technologies. This
technology uses coating method for taste masking.
The polymeric membrane eliminates the unpleasant
taste and / or odour. Offers advantages like precise
taste masking, good release profiles and patient
compliance.
Liquitard ODT Technology
This sophisticated Liquitard technology is
developed by APTALIS Pharmaceutical
technologies with an aim to provide an effective,
convenient, ready-to-use, taste-masked powder
formulation in single dose sachets that can be
administered as a suspension or sprinkle on easy to
swallow foods. This is developed with a wide
variety of flavours and is compatible with
customized release profiles.
Formulplex and Formulcoat
Pierre Fabre developed a new taste masking
technologies in which, coating of micro or nano-
sized particles at room temperature with non
organic solvent.
KLEPTOSE® Linecaps
Roquette offers a new taste-masking technology:
KLEPTOSE® Linecaps, uses a pea maltodextrin
for masking the bitter taste of drugs by decreasing
the overall amount of drug particles exposed to the
taste buds.
CONCLUSION
Taste masking of bitter drugs is a big challenge to
scientist. However we have made an attempt to
describe various methods, techniques suitable for
taste masking of obnoxious drugs. These
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techniques mentioned in this review can be used for
bench scale and pilot scale also.In addition to the
existing patented taste masking technologies,
several new technologies for effective taste
masking are also mentioned in this review. With
application of these techniques one can improve
product preference to a large extent.In addition to
oral drug delivery, the taste masked drug delivery
research is gaining importance for the quality of the
treatment provided to patients, especially children
and old. As evidenced by number of patients and
technology developments, an attempt of ideal taste
masking is widely accepted in the development of
palatable dosage forms having good patient
compliance without interfering the drug release.
Table 1: List of Threshold Concentrations for Primary
Taste Sensations on Specific Areas of Tongue5,7
Taste Threshold concentration Area of tongue
Sweet 0.5% Tip of tongue
Salt 0.25% Tip and sides of tongue
Sour 0.007% Sides of tongue
Bitter 0.00005% Back of tongue
Table 2: List of different types of polymers with examples6,8,10,11
Type of polymer
Examples
Water soluble polymers Cellulose acetate butyrate, polyvinyl pyrrolidone, hydroxyl ethyl cellulose
Water insoluble polymers Ethyl cellulose, polyvinyl avetate, crospovidone, cros caramellose
pH dependent Water insoluble polymers
Polycarbophil, polyacrylic acid
pH independent Water insoluble polymers Cellulose ethers, cellulose ester, polyvinyl acetate
Reverse enteric polymers Eudragit E 100, Eudragit EPO, methyl methacrylate, hydroxyl ethyl methacrylate, vinyl
pyridine
Enteric polymers Phthalate, hydroxyl phthalates, acrylic acid esters
Spacing layer polymers Ethyl cellulose : PVP
Table 3: Literature report on taste masking by coating16-28
Drug Category Coating material used
Acetaminophen NSAIDs Cellulose acetate(CA) or cellulose acetate butyrate(CAB) and
polyvinyl pyrrolidone(PVP)
Cefpodoxime
Proxetil Penicillin
antibiotics 1.Eudragit RD 100 in combination with Sodium CMC
2. Kollicoat IR
Desloratadine Anti allergic ethylcellulose(EC) and Eudragit EPO
Dextromethorphan Anti tussive EC:PVP and Eudragit E 100
Diphenhydramine
Hydrochloride
Anti histamines polyvinyl acetate and aminoalkyl
methacrylate copolymer
Ibuprofen NSAID EC and hydroxyethylcellulose(HEC) in Vaseline or silicon oil
Vitamins and
Minerals Diet Supplement Hydrophilic additives and poly vinyl acetate
Adipic acid and
Diet Supplement Reverse enteric polymer and acidic compound
Macrolide antibiotics Antibiotics Enteric coating polymer and osmotically active substance
NSAIDS NSAIDS Methacrylate ester co polymer
Cefuroxime axetil Penicillin antibiotics Acid soluble or swellable polymers, enteric polymer
Amobarbital Sedatives First water swelling gel forming layer and second water swelling
gel forming layer and adhesive layer
Ciprofloxacin
hydrochloride Fluoro Quinolone
antibiotics Nonionic and ionic polymers
Sildenafil citrate Vaso dilator HPMC, EC ( first coating layer), methyl or ethyl acrylate esters (
sec
ond coating layer ), sucrose ( third coating layer)
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Table 4: List of commonly used ion exchange resins5,8,10
Type of resin Functional
group Functional backbone Commercial resins
Strong anion -N
+
R
3
Polystyrene –DVB Amberlite IR 400, Dowex 1, Indion 454, Duolite AP 143
Weak anion -N
+
R
2
Polystyrene –DVB Amberlite IR 4B, Dowex 2
Strong cation -SO3H Polystyrene- DVB Amberlite IR 120, Dowex 50, Indion 244, Purolite C 100
HMR, Kyron –T-154
Strong cation -SO
3
Na Polystyrene- DVB Amberlite IRP 69, Indion 254, Tulsion-T-344
Weak cation -COOH Methacrylic acid- DVB Amberlite IRC 50, Indion 204-234, Tulsion 335, 339, Purolite
C 102DR, Kyron-T-104, Tulsion T 335, Doshion P544 ( R)
Weak cation -COOK Methacrylic acid- DVB Amberlite IRP 88, Indion 234, Tulsion T 339, Kyron-T-134
Table 5: Literature report on taste masking by Ion exchange resins8,10,29-41
Drug Category Dosage form Commercial Resin used
Chloroquine phosphate Anti malarial Indion cation exchange resin
Ciprofloxacin
Fluoro quinalones
Dextromethorphan hydrobromide Anti tussisive Dry/ Liquid
Suspension Carbomer 934
Ephedrine hydrochloride Sympathomimetic
drug Indion CRP 244/254
Erythromycin Macrolide antibiotic Liquid suspension Carbomer 934
Clarithromycin Macrolide antibiotic Liquid suspension Carbomer 934
Orbifloxacin Fluoro quinalones Antibiotic Dry / Liquid
suspension Amberlite IRP 64/69
Paroxetin hydrochloride Anti depressant Liquid suspension Amberlite IRP 88
Ranitidine hydrochloride Anti histamines Chewable tablet Amberlite IRP 69/88
Remacemide hydrochloride Anti parkinson’s drug Dry / Liquid
suspension Amberlite IRP 64
Erythromycin sterate Macrolide antibiotic Amberlite IR 120, Dowex 50, Indion
244
Dicyclomine hydrochloride Anti spasmodic Amberlite IR 120, Dowex 50, Indion
244, kyron-T-154, Purolite C 100
HMR
Spiramycin, dimenhydrinate,
roxithromycin,
Levocetrizine,Norfloxacin, Ofloxacin Amberlite IRP 50, Indion 204,
Purolite C 102 DR, Kyron-T-104,
Doshin P 544(R)
Metronidazole, Azithromycin, Quinine
sulphate, Paracetamol, Erdosteine Amberlite IR 4B, Dowex 2
Buflomedil Vasoactive agent Amberlite IRP 69
Chlorpheniramine maleate Anti histamines Indion CRP 244, Indion CRP 254
Clopidogrel sulphate Anti platelet drug Water soluble cation exchange resin
with sulfonic acid groups
Donepezil chloride Indirect Para
sympathomimetic
agent Anionic polymer and PVP
Sildenafil citrate Vaso dilator Anionic polymers ( Carragenan,
xanthan gum, dextran sulphate)
Table 6: List of commonly used sweeteners and
their relative sweetness42
Sweetening agent Relative sweetness Significance
Aspartame 200 Less stable in solution
Acesulfame potassium 137-200 Bitter in higher concentration
Cyclamate 40 Banned
Glycerrhizin 50 Moderately expensive
Lactose 0.16 High amount is required
Mannitol 0.60 Negative heat of solution
Saccharin 450 Unpleasant after taste
Sucrose 1 ( Standard ) Most commonly used
Sucralose 600 Synergestic sweetening effect
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Table 7: Classification of flavouring agents5,9
Type Example Significance
Natural Peppermint Less stable
Artificial Vanilla Highly stable
Natural and artificial Strawberry Effective at low concentrations
Table 8: Selection of flavours based on sensation of taste12
Sensation
Flavour
Salt Butterscotch, apple, apricot, peach, vanilla
Bitter Wild cherry, walnut, chocolate, mint, passion fruit
Sweet
Fruit and berry, vanilla
Sour Citrus flavours, liquorice, root bear, raspberry
Table 9: Literature report on taste masking by addition of flavours and sweeteners43-58
Drug Category Dosage form Taste Taste masking agent used
Eucalyptus oil Freshener Mouth wash Bitter Fenchone, Borneol
Ibuprofen NSAID Syrup,
Suspension Bitter Saccharin sodium, sucrose,
sorbitol
Thymol, triclosan Dental caries Oral rinses Bitter Citrus flavour, limonene
Zinc acetate dehydrate Zinc supplement Lozenges Bitter Saccharin sodium
Acetaminophen, Guaifenesin and
Dextromethorphan hydrobromide Sucralose , Citric acid
Aminoacids and proteins Diet supplement Sucralose
Dihydrocodeine phosphate, potassium
g
uaiacol sulfonate
Aspartame, Saccharin sodium,
Liquorice extract
Levofloxacin Fluoroquinolone
antibiotic Aspartame, Sucralose,
Saccharin sodium
Aspirin / Acetaminophen NSAID Menthol, Aspartame and or
Sucralose
Iron compounds Iron supplement Sucralose, sorbitol, Xylitol,
Maltitol or Erythritol
Mineral supplements Diet supplement Glycyrrhizin, Acesulfame
potassium
Vegetable crude drug Caramel
Vitamins Diet supplement Cacoa powder, Stevia extract,
Aspartame etc.
Pseudoephedrine Sympathomimietic
drug PEG with Sucralose
Table 10: Literature report on taste masking by inclusion complexation59-67
Drug Category Dosage form Complexing agent used
Zinc acetate dehydrate Recover zinc deficiency Anethol -β- cyclodextrin complex and saccharin
Carbapentane citrate Local anaesthetic Oral liquid Cyclodextrins
Ibuprofen NSAID Solution Hydroxypropyl β- cyclodextrin
Gymnema sylvestre
Anti
-
diabetic
Oral liquid
β
-
cyclodextrin, Chitosan
Dioscin CVS disorders β- cyclodextrin
Benexate hydrochloride
Antiulcer
Granules
β
-
cyclodextrin
Metronidazole benzoate Anti bacterial γ- cyclodextrin
Hexitidine
Anti bacterial
β
-
cyclodextrin
Zipeprol Anti tussive β- cyclodextrin
Guaiacol Anti diarrhetic β- cyclodextrin
Levosulpiride
Anti psychotic
β
-
cyc
lodextrin
Chloroquine phosphate Anti malarial Syrup Tannic acid
Dimenhydrinate
Anti emetic
Chewable tablet
Eudragit
-
S
-
100
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Table 11: Literature report on taste masking by prodrug approach8,10,68-70
Drug Category Modification done
Chloramphenicol Broad spectrum Antibiotic Palmitate or phosphate ester
Clindamycin Lincosamide antibiotic Alkyl ester
Erythromycin
Macrolide antibiotic
Alkyl ester
Lincomycin Lincosamide antibiotic Phosphate or alkyl ester
Tetracycline Broad spectrum antibiotic 3,4,5- trimethoxy benzoate salts
Triamcinalone Treatment of ulcerative colitis & skin disorders Diacetate ester
Table 12: Literature report on taste masking by microencapsulation71-88
Drug Category Dosage form Coating material used Technique used
Acetaminophen Anti pyretic Dispersible tablet Cross caramellose Wurster fluid bed
coating
Caffeine / Cimetidine Diuretic / anti histamine Chewable tablet Eudragit RL 30D, RS
30D
Wurster fluid bed
coating
Ciprofloxacin Fluoroquinolone
antibiotic Oily suspension,
sachets Eudragit NE 30D / RL
30D, HPMC Wurster fluid bed
coating
Levofloxacin Fluoroquinolone
antibiotic Suspension Eudragit E 100,
Cellulose acetate Wurster fluid bed
coating
Sildenafil citrate Vaso dilator Eudragit NE 30D, E 100 Top spray fluid bed
coating
Chlorpheniramine maleate Anti histamine Mouth melt
tablet Ethyl cellulose Top spray fluid bed
coating
Dextromethorphan
hydrobromide Anti tussive PVP-K30 Top spray fluid bed
coating
Acetaminophen Antipyretic Chewable tablet Eudragit E 100,
Cellulose ace
tate
Tangential spray fluid
bed coating
Theophylline Diuretic Dry suspension Eudragit NE 30D,
Guargum Tangential spray fluid
bed coating
Ampicillin trihydrate Penicillins Powders Sodium CMC Spray drying
Nizatidine Anti histamine Sprinkels Eudragit E 100 Spray drying
Roxithromycin Macrolides Suspension Eudragit RS 100/ RL
100 Spray drying
Clarithromycin Macrolides Powders Glyceryl monostearate,
Eudragit E 100
Spray congealing
Chloroquine di phosphate Anti malarial Powders Eudragit RS 100 Coacervation phase
separation
Metronidazole Anti amoebic Dry suspension Eudragit E, Fattibase Solvent evaporation
Ibuprofen, ketoprofen, aspirin
and Fenamic acid
NSAIDS Sodium alginate and
calcium salt
Solvent evaporation
Prazequantel Anti helmenthic Alginic acid and its salts Solvent evaporation
Isoprothiolane Antifungal Spray drying
Indeloxazine HCl Neuroprotective Fluidized bed drying
Table 13: Literature report on taste masking by granulation89-102
Drug Category Granulating agent used
Calcium compounds Mineral supplement Sugar alcohol
Erythromycin Macrolide Alginic acid
Dextromethorphan Anti tussive Cyclodextrin
Alprazolam Anxiolytic Eudragit E 100
Norfloxacin Flouroquinolone antibiotic Methacrylic acid ester
Macrolide antibiotic Macrolides
Polycarbophil
Ondansetron Anti nausent, antiemetic Polacrillin potassium
Ibuprofen Anti inflammatory Micro Crystalline Cellulose( MCC)
Granisetron HCl
Anti nausent, antiemetic
Glycerol behenate or glycerol palmitostearate
Levofloxacin Fluoroquinolone antbiotic Castor oil, sugar alcohol
Clopidrogel sulphate Anti platelet Castor oil, sugar alcohol
Telithromycin and pristinamycin
Macrolides
Glyceryl stearate or bees wax
Vitamins Diet supplement Polyglycerol ester of poly valent fatty acids
Penicillins, Macrolides Antibiotics Hydrogel or Wax
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Table 14: Literature report on taste masking by addition taste suppressants and or potentiators103-108
Drug Category Taste suppressant and / potentiator used
Bromhexine Mucolytic Thaumatin and sugar alcohol
Caffeine Diuretic Hydroxyflavones
Caffeine Diuretic Gamma-amino butyric acid
Paracetamol Antipyretic Potentiators: Glycyrrhizin, Thaumatin and neohesperidine dihydrochalcone ( NHDC)
Sweeteners: saccharin salts, acesulfame etc
Pioglitazone Anti diabetic Sodium chloride and coating with saccharides
Sugar alcohol
Nutritive agent
Aldehydes ( citral dimethyl acetal) and flavours
Table 15: Literature report on taste masking by liposomes and multiple emulsions5,8
Drug Category Taste masking agent used
Isoprothiolane Plant growth regulator Hydrogenated oil and HPMC
Acetaminophen NSAIDs Molten stearyl stearate
Talampicillin HCl Penicillin antibiotic Magnesium alluminium silicate and soya bean lecithin
Clarithromycin Macrolide antibiotic Glyceryl monostearate and AMCE
Indeloxazine HCl Cerebral activator Hydrogenated oil and surfactants
Table 16: List of evaluation parameters5,10
Subjective Methods Objective Methods
Preference test
Paired testing
Triangle testing
Hedonic scale
Difference test
Paired difference test
Triangle difference test
Duo trio test
Ranking test
Analytical test
Flavour profile
Time intensity test
Single attribute test
Dilution profile
Statistical test
Fig. 1: Structure of taste bud
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Fig 2, 3: Mechanism of taste perception
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Fig. 4: Classification of Coating materials6
Fig. 5: Electronic tongue
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... W literaturze znajdujemy różne metody, techniki i procedury opisujące maskowanie niekorzystnego smaku postaci leków. Wśród nich możemy wymienić m.in.: -dodatek aromatów i/lub substancji słodzących; -mikroenkapsulację; -żelowanie; -tworzenie kompleksów inkluzyjnych; -granulację; -emulsje wielokrotne; -żywice jonowymienne; -zastosowanie liposomów [8,9]. ...
... Są one częściej wykorzystywane niż związki naturalne. Występują w połączeniu z alkoholami cukrowymi, takimi jak sorbitol, maltitol i laktitol, w celu poprawienia parametrów organoleptycznych produktu i zwiększenia komfortu przyjęcia jednostkowej postaci preparatu przez pacjenta [9]. ...
... Podczas wyboru odpowiedniego sposobu maskowania nieprzyjemnego smaku substancji leczniczej, należy wziąć pod uwagę m.in. odczuwanie jej gorzkiego smaku (wskaźnik goryczy), sposób podania oraz zalecaną dawkę [9]. ...
Article
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Nieprzyjemny smak, którym charakteryzuje się liczna grupa substancji leczniczych może stanowić wyzwanie zarówno dla naukowców na etapie projektowania określonej postaci leku, jak również dla pacjenta podczas przyjmowania danego preparatu. Wrażenia smakowe pełnią istotną rolę w dzisiejszych czasach, będąc niekiedy jednym z kryteriów wyboru, którym kieruje się pacjent podczas wizyty w aptece ogólnodostępnej oraz mogą one wpływać na pozytywny odbiór preparatu i w efekcie udaną komercjalizację produktu leczniczego. Doznania smakowe pełnią kluczową rolę w przypadku doustnych postaci leku, a przede wszystkim rozpuszczalnych postaci oraz pozostałych płynnych form leków. Główną grupą docelową płynnych preparatów leczniczych są pacjenci pediatryczni oraz osoby mające problem z połykaniem stałych doustnych postaci leku, a także seniorzy. Zwłaszcza dzieci stanowią grupę pacjentów, dla których walory smakowe są niezwykle istotne. Substancje lecznicze charakteryzujące się nieprzyjemnym smakiem i/lub zapachem, poprzez niską akceptację ze strony pacjenta mogą także oddziaływać na zmniejszenie skuteczności procesu leczenia. Skuteczne zamaskowanie nieprzyjemnego smaku substancji leczniczej jest możliwe dzięki rozwojowi wielu technik umożliwiających ten proces, co z kolei może znaleźć przełożenie na bardziej regularne przyjmowanie leków przez pacjenta wg odpowiednich zaleceń. Maskowanie nieprzyjemnego smaku API (ang. Active Pharmaceutical Ingredient) można osiągnąć za pomocą różnych metod. Celem artykułu jest omówienie kilku najpopularniejszych, a mianowicie wykorzystujących dodatek aromatów i/lub substancji słodzących, mikroenkapsulację, zmiany reologiczne, tworzenie kompleksów inkluzyjnych, granulację, emulsję wielokrotne, żywice jonowymienne oraz zastosowanie liposomów. Należy zaznaczyć, że wybór odpowiedniej metody powinien być ukierunkowany kilkoma aspektami, w tym przede wszystkim właściwościami fizykochemicznymi stosowanej substancji leczniczej, częstotliwością dawkowania, a także postacią leku.
... This is the simplest and most convenient method of taste-masking. Sweeteners can be coated on bitter medications to enhance the flavor of the base material [29]. As described in Table 2, sweeteners can be classified as natural or artificial depending on their source [30]. ...
... Granulation has unique characteristics against all the above discussed techniques, such as low cost, faster, and easily scalable taste masking method is widely used for taste masking properties [1]. In this method, insoluble polymers are used for granulation process which is used in tablet manufacturing because they are insoluble in saliva and cover the unpleasant taste of drugs [29]. Literature has been compiled in the section below on masking the taste via granulation technique. ...
... The most often utilized adsorbent is active carbon, which is particularly well suited for the removal of apolar molecules. Adsorbates such as silica gel, bentonite, and veegum are used to adsorb the drug solution [29]. Researchers developed a tastemasked loperamide formulation with magnesium aluminum silicate by combining the drug with the adsorbate and then granulating with water-insoluble polymers to achieve taste masking [80]. ...
Article
One of the important parameters in the case of dosage form is taste. Most of the drugs available in oral dosage form have an unpleasant taste which leads to patient incompliance and affects the success ratio of products in market. Geriatric and paediatric patients suffer more with a bitter taste of medicines. According to the studies reported, it is found that 50% of the population have problem of swallowing tablets, especially the pediatric and geriatric population. Masking the taste of bitter drugs has become necessary in the pharmaceutical field and increasing interest of researchers to develop various methods for masking the bitter taste of drugs. Five major tastes that are felt by our tongue are salt, sour, sweet, bitter and umami. When the drug dissolves with saliva, drug molecules interact with taste receptors present on the tongue and give taste sensations. Although many solid oral dosage forms like pills, tablets have additional advantage of masking and encapsulation of bitter taste drugs but they might not be effective for children because they may or may not swallow pills or tablets. There are various other methods that masks the bitter taste of drugs such as addition of sweeteners and flavouring agents, granulation, coating, inclusion complexes, extrusion method, ion-exchange resins etc, discussed in first section of article. The second part of this article consists of various nanotechnology-based drug delivery systems that were fabricated by researchers to mask the bitter taste of drugs. A brief of recent literature on various nanocarriers that were fabricated or developed for taste masking has been discussed in this part. A better understanding of these methods will help researchers and pharmaceutical industries to develop novel drug delivery systems with improved taste masking properties.
... Administration of unpalatable drugs is hampered by their unpleasant taste particularly in case of pediatric and geriatrics. 1,2 Taste masking is defined as a perceived reduction of an undesirable taste that would otherwise exist. The ideal solution to reduce or inhibit bitterness is the discovery of a universal inhibitor of all bitter tasting substances that does not affect the other taste modalities such as sweetness or saltiness. ...
... In addition to oral drug delivery, the taste masked drug delivery research is gaining importance for get better the quality of the treatment for paediatrics and geriatrics. 2,3 Factors that are taken into consideration during the taste masking formulation include. 2 • Extent of the bitter taste of the API • Required dose load • Drug particulate shape and size distribution • Drug solubility and ionic characteristics • Required disintegration and dissolution rate of the finished product • Desired bioavailability • Desired release profile Types and mechanism of taste 1,2,4 Taste is one of the usual five senses and is the capability to detect the flavor of substances such as food, certain minerals, and poisons, etc. It decides the selection of food, its palatability and stimulation of reflexes for secretion of saliva, gastric juices and pancreatic juices. ...
... 2,3 Factors that are taken into consideration during the taste masking formulation include. 2 • Extent of the bitter taste of the API • Required dose load • Drug particulate shape and size distribution • Drug solubility and ionic characteristics • Required disintegration and dissolution rate of the finished product • Desired bioavailability • Desired release profile Types and mechanism of taste 1,2,4 Taste is one of the usual five senses and is the capability to detect the flavor of substances such as food, certain minerals, and poisons, etc. It decides the selection of food, its palatability and stimulation of reflexes for secretion of saliva, gastric juices and pancreatic juices. ...
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Dicyclomine hydrochloride is anticholinergic drug used as an antispasmodic. It is very bitter in taste. The purpose of this research was to reduce the bitterness of Dicyclomine hydrochloride. Taste masking was done by complexing Dicyclomine hydrochloride with β Cyclodextrin. Drug β-Cyclodextrin complexes were prepared in the ratio 1:1, 1:2 and 1:3 by kneading method. The complexes were characterized by Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) patterns. These studies indicated the inclusion of Dicyclomine in the cavity of β-cyclodextrin. The 1:3 complexation ratio resulted in mask of taste of dicyclomine was selected as it showed acceptable taste and for further use in mouth dissolving oral formulations.
... • By adding some traditional material like alkaline earth oxide ,alkaline earth hydroxide has proved effective for masking the bitter nature of chemical. 8 • Natural flavors are the most common type of taste found in food and pharmaceutical products. They are however being phased out in the flavor of synthetic flavor due to numerous drawbacks, including unpredictability in standard due to natural origin, unreliability, expense, and reachability. ...
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Taste is the ability to determine the flavor of substances like food, drug, etc. The aspect of taste only occurs when the drug get soluble in saliva. Firstly the drug gets dispersible in saliva then they show interaction with taste bud and then perception of taste is occurred. The above test receptor get binds to the molecules of saliva and generates the electrical impulses from the area of brain that area is cranial nerves 7th ,9th 10th and then perception of taste occurs. Currently varieties of drugs are available like cardiac, analgesic, anti-inflammatory, opioid analgesic, anti-epileptic, anticoagulant, oral vaccine and sex hormone. Due to bitter formulation it tends to patient complain the problem of bitter and unpleasant taste of drug in the pediatrics and geriatric formulation is provocation to the pharmacist in the current scenario .Bitter taste masking become important to solve patient complain. This is become most important issue regards with pharmaceutical therapies. Taste masking get broadly classify into physical, chemical, biochemical and organoleptic methods. There are different types of method are available to mask the unpleasant taste of drug. The physical method involves the use of sweeteners and flavor enhancers. The chemical method involves Ion exchange resin, solid dispersions, spray drying, Inclusion complex, Microencapsulation, coating. The biochemical method involves Prodrug, Hot melt extrusion. The most abundantly used method involves are spray drying, Inclusion complex, Microencapsulation, coating, hot-melt extrusion, and organoleptic methods. Keywords: Obnoxious, Hot melt Extrusion, Ion exchange resin, coating, palatability.
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Especially for patients who have dysphagia or difficulty swallowing, oral disintegrating tablets (ODTs) have developed as a novel dosage form to address a number of issues related to traditional solid dosage forms. An overview of the formulation techniques, assessment criteria, and uses of ODTs in pharmaceutical research are given in this study. In order to accomplish quick disintegration and dissolution of the tablet matrix upon contact with saliva, formulation processes such as sublimation, lyophilization, and direct compression have been thoroughly investigated. When evaluating the quality qualities of ODTs, evaluation metrics such as drug content homogeneity, hardness, friability, and disintegration time are essential. To improve patient acceptance and palatability, superdisintegrants and a variety of taste-masking techniques have been used. Furthermore, ODTs adaptability goes beyond traditional oral administration they may be used for emergency and travel medicine, as well as in paediatric and geriatric populations. All things considered, ODTs present a viable platform for enhancing patient convenience and compliance, which maximises therapeutic results. ODTs provide a number of benefits, such as improved patient compliance, simplicity of administration, and greater bioavailability because of their quick dissolving and larger surface area. To sum up, oral disintegrating tablets offer a potentially effective option for individuals who need readily administrable and comfortable dose forms. ODTs will be further optimised by ongoing research and development into manufacturing and formulation processes, increasing their applicability to a wider range of patient demographics and therapeutic areas.
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Introduction and purpose: The unpleasant extremely bitter taste of the orally administered broad-spectrum antibiotic azithromycin decreases patient compliance, especially in pediatrics. This issue can be overcome by decreasing drug interaction with the tasting buds using insoluble polymers at salivary pH (6.8 - 7.4), like the cationic polymer Eudragit EPO. Supercritical fluid technology is a green synthesis method for preparing pharmaceutical preparations that replace organic solvents with safe supercritical CO2. This study aimed to mask the bitter taste of azithromycin using the supercritical fluid method and a pH-sensitive Eudragit EPO polymer. Methods: A foaming process was investigated for preparing a formulation (TEST), which comprises treating the polymer with supercritical carbon dioxide (CO2) fluid to prepare a taste-masked dosage form without employing organic solvents or flavors. Results: The use of the supercritical technique at 40 °C and 10 MPa for 2 h allowed the manufacturing of solvent-free polymeric foam with azithromycin dispersions; the average calculated percentage of apparent volume change was 62.5 ± 5.9% with an average pore diameter of 34.879 Å. The formulated sample showed low drug release in simulated salivary fluid while keeping its crystalline nature. Moreover, clinical studies on healthy subjects showed that the formula successfully masked azithromycin's bitter taste. Conclusions: Overall, it has been shown herein that the supercritical fluid technology foaming method is promising in masking the bitter taste of bitter ingredients.
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The problem of bitter and obnoxious taste of drug in pediatric and geriatric formulations is a challenge to the pharmaceutical industry in the present scenario. Taste is an important factor in the development of dosage form and it is that parameter of product development which has been curiously studied and developed by the researcher for its importance. Taste masking technologies offer a great scope for invention and patents. Taste masking ensure better patient compliance for bitter or objectionable taste of drugs formulations as this desirable aspect will provides commercial gains to pharmaceutical industries due to higher market demand of products, patent protection to novel taste masked formulations and also for exclusive marketing rights. The logical objective of present review is to explore and compile different method, technologies for specic dosage forms and evaluations techniques of taste masking the obnoxious taste of drugs for better patient suitabilit
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Scientists struggle to conceal the bitterness of medications. Many oral medicines and bulking agents are bitter. Bitterness masking is vital for patient compliance. Many formulations with increased performance and acceptance have been developed to improve palatability. The disagreeable taste of formulation has been disguised by sensory, barrier, chemical, and complexity methods. Taste is acknowledged as a crucial component in patient compliance, especially in youngsters, where acceptability and hence ease of administration may be considerably altered. The methods used to hide the taste of medications are detailed in this review. Taste is a key factor in oral product adoption. Many oral medications, foods, and bulking agents have unpleasant bitter flavours. Oral administration of bitter medications is a major concern for health care practitioners, particularly for juvenile patients. Masking a drug’s disagreeable taste increases patient compliance and thereby profits. Various known procedures have been used to remove or reduce the bitterness of these medications, but no generally applicable methodology has been identified.
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Metronidazole benzoate, an antiprotozoal drug, forms a 1:1 (mol:mol) inclusion compound with gammacyclodextrin. Phase-solubility analysis, differential scanning calorimetry, X-ray diffraction on powder, and infrared spectra were used in order to characterize the inclusion compound both in solution and in the solid state. The stability of the drug to alkaline hydrolysis was improved in aqueous solutions of gamma-cyclodextrin.
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Solutions to drink for gut lavage have an unpleasantly salty taste, that can, in the worst case, cause the rejection of an indicated colonoscopy by the patient. But the commonly used lavage solutions containing polyethylenglycol are indeed difficult to aromatise. We propose a lemon flavour formulated as a gel for facilitating both production and application. The gel quickly dissolves in the lavage solution. Our lemon flavour contains sugar; therefore diabetics, who do not accept the lavage solution without aroma, have to be treated with additional insulin. In more than 10 000 colonoscopies - prepared with our aroma- we have never seen events possibly caused by formation ofoxyhydrogen.
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Chloroquine phosphate is a bitter antimalarial drug belonging to the 4-amino quinoline class of compounds. It was treated with tannic acid and precipitated to form a poorly soluble complex. The complex was analysed and evaluated for taste and in vitro release. It was then formulated in a syrup base. When orally administered to healthy human subjects, chloroquine level comparable to marketed preparation was obtained. On the basis of the preliminary results obtained in the present study the method may be further evaluated as a technique for taste masking of bitter amine drugs.
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Oral administration of pharmaceuticals is one of the most popular method of drug dilevery. Many orally administered drugs elicit bitter taste. Palatability is an extremly important factor in ensuring the likelihood that the recepient will intake the pharmaceuticals. A constant problem is in treatment of patient is their inability or unwillingness to swallow solid dosage form such as tablets specially in children and the elderly. These dosage form permit perceptible exposure of active drug ingredient to the taste bud. Accordingly, masking of unpleasent taste characterstics of drug is an important factor in formulation of these agents."The worse the taste of the medication, the better the cure" was once the prevailing attitude. Today a change in patient attitude and development of taste masking technique has reversed this opinion. Patients now expect and demand formulations that are pleasently, or atleast tolerably, flavored.1 This article reviews the earlier methodologies and approaches of taste masking of bitterness reduction.
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A method of taste-masking using a spray-congealing technique was developed. Clarithromycin (CAM), a macloride antibiotic with a bitter taste, was selected as the model compound. The fundamental objective was to prevent the preparation from dissolving in the mouth, while ensuring that rapid release of CAM from the preparation could be attained in the gastrointestinal tract, resulting in bioequivalence to the conventional dosage form. Glyceryl monostearate (GM) and aminoalkyl methacrylate copolymer E (AMCE) were selected as ingredients, since GM, a substance with a low melting point, is able to be decomposed by an enzymatic reaction in the intestinal tract where the solubility of AMCE is very low. On the other hand, AMCE was selected because it is freely soluble at low pH levels (e.g. the pH level in the stomach), but insoluble in neutral and high pH levels (e.g. the pH level in the mouth). Spherical particles of the matrix (spherical matrix) and disks of matrix with various ratios were prepared, and the optimum ratios of CAM, GM and AMCE for the following release criterion were determined by experimental design (the simplex method). That is, 100 mg/l of CAM in the spherical matrix should be completely released within 20 min in pH 4.0, and less than 14 mg/l of CAM in spherical matrix should be released at 60 min in pH 6.5. As a result, the optimum formula for the matrix in consistency with the criterion was 3:6:1 for CAM, GM and AMCE, respectively.