A

Seminar on
Review On: Taste Masking
Approaches' & Evalution.

Presented by
Sagar B. Thoke
M. Pharm IInd Semester
[Dept. of Pharmaceutics]
Guided by
Prof . Y. P. Sharma
Contents :-

 The human tongue- Anatomy & Physiology

 Problems arise in taste masking
 Ideal taste masking process and formulation properties
 Factors consideration during the taste masking
 Approaches to Unpleasant Taste Inhibition
 Evaluation of Taste Masking Effect
 References

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 The human tongue :-
Organ for taste, help in speech, swallowing.

 Anatomy & Physiology of the Tongue :-

Tongue Muscles
 Intrinsic muscles
 Extrinsic muscles
Vasculature
receives blood supply primarily from the lingual artery, which
drain into internal jugular vein.
Length-from the oropharynx to the tip is 10 cm (4 in).
Tongue physiology
The chemicals bind their particular receptors and initiate
signaling that travels through the nerves to the brain, where they
are interpreted.

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Fig. Taste Points in Tongue Fig. Physiology of Taste Bud

Taste Chemical
Salty Ions (ex: sodium)
Sweet Sugars, ketones, aldehydes, some amino acid
Sour Acidic compounds
Bitter Not yet known, possible link to toxicity
Umami (savory)* L-glutamate/glutamic acid
 Fifth taste bud type discovered in 2002.
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Taste Signaling Pathways
Taste transduction begins with the interaction of a tastant (eg.
medicine or food) with taste receptor cells in the taste buds8 (Fig ).
The tastant binds with G-Protein coupled receptors (GPCRS) in the
cells triggering the release the release of G-Protein called
Gustducin.

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Taste Blocking Mechanism
Taste sensation begins when Gustducin
activates the effector enzymes
phosphodiesterase IA (PDE) or phospholipase
C beta-2(PLC).
The effector enzyme then changes the
intracellular level of second messenger such as
cyclic adenosine monophosphate (cAMP),
Inositol, 1, 4, 5- triphosphate (IP3) and
diacylglycerol (DAG).
The second messengers activate calcium ion
channel inside the cell and sodium, potassium
and calcium channel on extra cellular
membrane.
Ionization depolarizes the cell causing release
of neurotransmitters that send nerve impulses
to the brain that carries the signal of bitter taste
and taste blockers work by interfering with
taste transduction.
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Taste refers to a perception arising from the stimulation of taste
buds.

Undesirable taste- problems in formulation & patient

compliance.

Children, older persons, trouble swallowing tablets or capsules.

chewable solid form (sublingual or buccal tablets), liquid form

or ODT.
Taste of Ciprofloxacin mask by sodium saccharin in ODT.

Taste masking- reduction of an undesirable taste.

 Problems arise in taste masking :-

 Inadequate taste masking
 Coating- imperfections, if present, reduce the efficiency.

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 Ideal taste masking process & formulation properties :-

1) Involve least number of equipment's and processing steps.

2) Require minimum number of excipients for an optimum
formulation.
3) No adverse effect on drug bioavailability.
4) Least manufacturing cost.
5) Can be carried out at room temperature.
6) Require excipients that are economical, easily available with
high margin of safety.
7) Rapid and easy to prepare.

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 Factors consideration during the taste masking :-
1) Extent of the bitter taste of the API.
2) Required dose load.
3) Drug particulate shape and size distribution.
4) Drug solubility and ionic characteristics.
5) Required disintegration & dissolution rate of finished
product.
6) Desired bioavailability.
7) Desired release profile.
8) Required dosage form.

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Taste masking patents and patent applications are contributed from

 Asia-49.34%

 North America- 41.45% of

which 62.67% were filed
in USA and

 Europe- 9.30%

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 Taste masking technology filed in the period of year 1997
to 2007.
(% contribution of each different taste masking technologies
Calculated.) 5/17/2012 11
Fig. Taste Masking Technologies uses in liquid and solid dosage forms

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 Approaches to Unpleasant Taste Inhibition :-

1. Taste masking with flavors, sweeteners, and amino acids

2. Taste Masking by Inclusion Complexation
3. Taste Masking by Ion-Exchange Resins (IERs)
4. Taste Masking by Microencapsulation
5. Solid dispersion
6. Mass extrusions
7. Multiple Emulsions
8. Wax Embedding of Drug
9. Development of Liposome
10. Taste masking by adsorption
11.Taste masking by Prodrug approach
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12. Taste Masking with Lipophilic Vehicles like lipids and
lecithins
13. Taste Suppressants and Potentiators
14. Granulation
15. pH Modifiers
16. Freeze Drying Process
17. Viscosity Modifications
18. Salt Preparation
19. Taste masking by gelation

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1. Taste Masking with Sweeteners and Flavours
1. Flavors
Natural Flavors Synthetic Flavors
 Juices - Raspberry  Alcoholic solutions
 Extracts - Liquorices  Aqueous solutions
 Spirits - Lemon & Orange  Powders
 Syrups – Blackcurrant
 Tinctures -Ginger
 Aromatic waters - Anise & Cinnamon
 Aromatic Oils – Peppermint & Lemon.

Natural Vs Synthetic
 Cheaper
 More readily available
 Less variable in chemical composition
 More stable

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Basis of Choosing a Flavor
 Complementary to existing flavor of the drug
 Known popularity of particular flavors
 Age of patients
 Allergy
Flavoring agents for taste masking
Basic Taste Masking agents
Salt Butterscotch, maple, apricot, peach, vanilla,
wintergreen mint.
Bitter Wild cherry, walnut, chocolate, mint, anise.
Sweet Vanilla, fruit and berry.
Sour Citrus flavor, licorice, root beer, raspberry.

2. Sweetners
 Complement flavors associated with sweetness
 Soothing effect on the membranes of the throat

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Natural Artificial Nutritive Polyols Novel
Sweetener Sweetener Sweeteners Sweeteners
Sucrose, Saccharin, Sucrose, Mannitol, Trehalose,
Glucose, Saccharin Fructose and Sorbitol, Tagatose
Fructose Sodium Glucose Xylitol,
Sorbitol, Aspartame Erythritol,
Mannitol, Maltitol.
Glycerol
Honey,
Liquorice

Taste masking of water soluble bitter drugs, with a high dose, is

difficult to achieve by using sweeteners alone.

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List of FDA approved Non-Nutritive sweeteners
Sweeteners Sweetness factor, Sucrose=1
Aspartame 180-200
Sucralose 600
Acesulfame K 200
Neotame 7,000-13,000
Saccharin 300

3. Amino Acids and Protein Hydrolysates

combining amino acids or their salts with bitter drugs, reduce the
bitterness.
Amino acids- sarcosine, alanine, taurine, glutamic acid, and
glycine.
Ampicillin granules with glycine and mixing them with additional
quantity of glycine, sweeteners, flavors.

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2. Taste Masking by Inclusion Complexation
Drug molecule fits into the cavity of a complexing agent, i.e. the
host molecule, forming a stable complex.
Vander Walls forces are mainly involved in inclusion complexes.

low stability constant lead to a rapid release of free drug

Hydrophobic drugs form complex by replacing „inclusion water‟
while easily migrating (hydrophilic, well soluble) drugs form
complex, assuming replacement of „crystal water‟.
β-cyclodextrin- sweet, non-toxic, cyclic oligosaccharide obtained
from starch.
 Decreasing its oral solubility on ingestion or
 Decreasing the amount of drug particles exposed to taste
buds
Suitable only for low dose drugs.
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3. Taste Masking by Ion-Exchange Resins (IERs)
 High molecular weight polymers With cationic and anionic
functional groups
 Ability to exchange counter-ions within aqueous solutions
surrounding them.
 small (1-2 mm diameter) beads with pores structure.
Classification
A. Cation Exchange Resin
a) strong cation exchanger contains sulphuric acid sites
b) Weak cation exchangers based on carboxylic acid moieties.
B. Anion Exchange Resin
a) strong anion exchange resins have quaternary amine ionic sites
attached to the matrix,
b) weak anion exchanger has predominantly tertiary amine
substituents.
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 Drugs are attached to the oppositely charged resin substrate, by
weak ionic bonding form insoluble complex.

 which does not dissociates the drug-resin complex at salivary

pH conditions.

Drug release depends on-

properties of the resin and the ionic environment within the GIT.

Cation exchange or weak anion exchange resins

examples of IER – drug complex

Resin Medicament
Name Functionality Polymer backbone
AmberliteTM Weak acid Crosslinked Dextromethorphan,
IRP64 COO- polyacrylic Dimenhydrinate
AmberliteTM Strong acid Styrene-Divinyl Ranitidine
IRP69 SO3- Benzene
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AmberliteTM Weak acid Crosslinked Talampacillin-HCl,
IRP88 COO- polyacrylic Paroxetine
Indion 204 Weak acid Crosslinked Norfloxacin,
COO- polyacrylic Ofloxacin
Indion 214 Weak acid Crosslinked Azithromycin
COO- Polyacrylic
Indion 234 Weak acid Crosslinked Ciprofloxacin,
COO- Polyacrylic Chloroquin
phosphate
Kyron T-104 Weak acid Crosslinked Cefpodoxime,
COO- polyacrylic proxetil
Kyron T-114 Weak acid Crosslinked Ofloxacin
COO- Polyacrylic
Kyron T-134 Weak acid Crosslinked Metronidazole
COO- polyacrylic

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4. Taste Masking by Microencapsulation
process by which very tiny droplets or particles of liquid or solid
material are surrounded or coated with a film or polymeric
material.

Coating created a physical barrier between the drug and the taste
buds. Reduce its solubility in saliva and thus mask taste.
Factors to be consider
 completely mask the taste of a bitter drug, &
 not adversely affecting the intended drug release profile.
Polymers used for coating-
water insoluble polymers- cellulose ethers, cellulose ester,
polyvinyl acetate
water soluble polymers- cellulose acetate butyrate, PVP,
hydroxyethyl cellulose

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5. Solid Dispersions
as dispersion of one or more active ingredients in an inert carrier or
matrix at solid state
prepared by melting (fusion) solvent or melting solvent method.
Amine or amido group of dimenhydrinate can have a physical and
chemical interaction with the carboxylic acid and esters groups.
Natural copolymers- shellac, zein and cellulose acetate phthalate
hydrophobic polymers and long chain fatty acids.

enteric polymers like derivatives of acrylic acid polymers and

phthalate are good choices
requires a higher concentration of excipients compared to other
techniques
7. Multiple Emulsions
Bitter taste of chloroquine was masked in o/w/o and w/o/w
emulsion system.
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9. Development of Liposome
Masking the unpleasant taste of therapeutic agent by entraping
them into liposome.
Incorporation of drug into liposomes prepared with egg
phosphatidyl choline masked the bitter taste of antimalarial,
Chloroquine phosphate in HEPES (N-2- hydroxyethylpiperzine-
N'-2 ethane sulfonic acid) buffer at pH 7.2.
10. Taste masking by adsorption
Adsorbate of bitter tasting drug less saliva soluble.
Preparing a solution of the drug and mix with an insoluble powder
that will adsorb the drug, remove the solvent, dry it.
Veegum, bentonite, silica gel and silicates used as adsorbate.
Ranitidine with a synthetic cation exchange resin adsprbate.
Loperamide and phenyl propanolamine adsorbed on magnesium
aluminium silicates (Veegum F) form taste masked suspension.
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11. Taste masking by Prodrug approach
Prodrug - chemically modified inert drug precursor which
upon biotransformation liberates pharmacologically active
parent compound.
reducing solubility, and thereby improving taste.
Bitterness of a molecule due to the efficiency of taste receptor
substrate adsorption reaction, which is related to the molecular
geometry of the substrate.
By derivative formation, the geometry is altered, affecting the
adsorption constant.

changing the molecular configuration of the parent molecule

change Magnitude of a bitter taste.
Nalbuphine HCL, naltrexone, naloxone, oxymorphone HCL,
butorphanonol, and levallorphan tasteless prodrug for buccal
administration.
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 Parent Drug Prodrug
Erythromyci Erythromycin Propionate
Clindamycin Clindamycin palmitate ester
Chloramphenicol Chloramphenicol palmitate ester
Morphine N-oxide derivatives of all Morphine
Triamcinolone Triamcinolone diacetate ester

18. Salt Preparation

Adding alkaline metal bicarbonate (sodium bicarbonate) masks the
unpleasant taste of water -soluble ibuprofen salts in aqueous
solution.
Penicillin prepared as N, N-di benzyl ethylene diaminediacetate
salts or N, N-bis (deyhdroabiety) ethylene diamine salts is
tasteless.

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13. Taste Suppressants and Potentiators
Linguagen’s bitter blockers (e.g. adenosine monophos-phate)
compete with bitter substances to bind with the G-protein
coupled(GPCR) receptor sites.
Hydrophobic nature of drug contributes to binding and inter-
action with the receptor sites.
Suppressants
Lipoproteins are universal bitter taste blockers.
lipoproteins composed of phosphatidic acid and β-lactoglobulin
inhibit the taste nerve responses to the only bitter substances.
Phospholipid (BMI-60)
Neohesperidine phospholipids- interact chemically with the taste
receptors.
Cooling and warming agents- extreme sensations to overpower
the bitter taste and confuse the brain.
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Thymol taste mask by mixture of cooling (e.g. eucalyptol) and
warming agents (e.g. methyl salicylate).
Potentiators- increase the perception of the taste of sweeteners.
Potentiators Sweeteners
Thaumatine, neohesperidine sodium or calcium saccharinates,
dihydrochalcone (NHDC) and saccharin, aspartyl-pheny-
glycyrrhizin lalanine, acesulfame, cyclamates,
and stevioside.

Bromhexine- Thaumatine with sugar alcohols mask taste.

Bitter taste blockers- Hydroxy flavanones, adenosine
monophosphate and γ-amino butanoic acid.
Desensitizing agents- desensitize the taste buds by interfering
with taste transduction.
e.g. phenols, sodium phenolates
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15. pH Modifiers
The enteric polymers (eudragit L) solubilize at pH beyond pH 5.5
& pH of saliva 5.8. possibility of drug partially leached.

pH Modifying agents- generating a specific pH

microenvironment & facilitate in situ precipitation of bitter drug
in saliva, reducing taste sensation.
L-arginine maintains alkaline pH of the vehicle to promote
precipitation of des-quinolone in saliva.

16. Freeze Drying Process

Zydis and Lyoc technology- drug is physically entrapped in
matrix composed of saccharide e.g. mannitol and a polymer
piroxicam, loperamide, ondansetron, chlorpheniramine are
various drugs taste-masked by Zydis technology.

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17. Viscosity Modifications
Increasing viscosity with gums or carbohydrates can lower the
diffusion of drug.
decrease contact between bitter drugs and the taste receptors.
thickening agents such as PEG and NaCMC.
Acetaminophen suspension with xanthan gum (0.1‐0.2%) and
microcrystalline cellulose (0.6‐1%).
Gelatine and flavours (chocolate flavour) mask the bitter taste of
tannic acid by viscosity effects, form jelly on cooling.

8. Wax Embedding of Drug

Tastes masked by embedded granules of ephedrine HCl,
Chlorpheniramine maleate, Diphenhydramine HCl were prepared
in stearic acid & other waxes.

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 Evaluation of Taste Masking Effect

tedious work as the taste sensation varies person to person.

coated microsphere & Ion exchange resin- drug release rate can
serve as an index of the degree of masking achieved.
 Sensory evaluation
It is possible to accurately and reproducibly measures taste
thresholds.
To quantitatively evaluate taste sensation, following methods used
1. Panel testing (human subjects)
2. Measurement of frog taste nerve responses.
3. Multichannel taste sensor/ magic tongue
4. Spectrophotometric evaluation/ D30‟s value

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1] Panel Testing
 In vivo Evaluation
 The panel testing is a psychophysical rating of the gustatory
stimuli.
 5‐10 human volunteers with organoleptic sense.
 reference solutions ranging in taste from tasteless to very
bitter.
 Normal dose was held in mouth for 60 seconds.
 Bitterness recorded against pure drug (test solution) is tasted
and rated on the same numerical scale to assess its bitterness.
Numerical values are then assigned to these levels of bitterness
(eg.,0‐5).
0 = pleasant,
1 = Tasteless,
2 = No bitter but after taste give bitterness,
3 = immediately gives bitterness,
4 = slightly bitter,
5 = extremely bitter.
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 Demands large panels and elaborate analysis, raises safety and
scheduling issues and
 Time consuming and expensive.

2] Measurement of Frog Taste Nerve Responses

Adult bull frogs glossopharyngeal nerve is located and dissected

from the surrounding tissue and cut proximally

An ac‐amplifier and an electronic integrator used to amplify and

integrate the nerve impulses.

The peak height of the integrated response is then taken as the

magnitude of response.

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3] Multichannel Taste Sensor / Magic tongue
In vitro Evaluation
“E-Tongue” automated taste sensing device- detect magnitude of
bitterness. Overcomes problems of panel testing.

recognition, quantitative multicomponent analysis and artificial

assessment of taste and flavour.
It recognizes three levels of biological taste including
1] Receptor level (Taste buds in humans, probe membranes in E-
Tongue),
2] circuit level (neural transmission in humans, transducer in E-
Tongue), and
3] perceptual level (cognition in the thalamus humans, computer
and statistical analysis in the E-Tongue).
Transducers composed lipid/polymer membranes to detect taste as
like to human gustatory sensation.

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Probes consist of a silicon transistor with proprietary organic
coatings, which govern the probe‟s sensitivity and selectivity, and
measurement done potentiometrically.
statistical software interprets the sensor data into taste patterns.
Liquid samples directly analysed, solids require to dissolve.
Reference electrode and sensors are dipped in a beaker
containing a test solution for 120 seconds (as shown in fig.).

A potentiometric difference between each sensor and a

reference electrode measured and analyzed by software.

e.g. Quantification of Suppression of bitterness of Quinine by

sucrose.

E-Tongue enables us to test taste accurately without the need for

human volunteers at earlier stages.
E-Tongue lose its sense of taste after long periods of testing
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Fig. : Evaluation of taste using e-tongue
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4] Spectrophotometric Method

 A known quantity of the taste‐masked formulation is mixed

with 10 ml of distilled water in 10 ml syringe by revolving the
syringe, end to end, five times in 30 seconds.

 test medium then filtered through a membrane filter, followed

by spectrophotometric determination of the concentration of the
drug in the filtrate.

 If this concentration is below the threshold concentration, it

may be concluded that the bitter taste would be masked in vivo.

 This technique has been applied to evalute the taste masked

granules of sparfloxacin, with threshold concentration being
100μg/ml.

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 References
 K.P. Sampath Kumar, THE PHARMA INNOVATION-Taste Masked
Suspension, www.thepharmajournal.com, Vol. 1 No. 2 (2012), Page no.- 1-6.

 Nilesh Jain, Effect of superdisintegrants on formulation of taste masked

fast disintegrating Ciprofloxacin tablets, International Current Pharmaceutical
Journal 2012, 1(4): Page no.- 62-67.

 Velmurugan S, Oral Disintegrating Tablets: An Overview, International

Journal of Chemical and Pharmaceutical Sciences 2010, Dec., Vol.1 (2): Page
no.- 1-10.

 A. M. Suthar, Ion Exchange Resin As An Imposing Method For Taste

Masking: a Review, An International Journal of Pharmaceutical Sciences,
Vol-1, Issue-2, (2010), Page no.- 6-10.

 Aditi Tripathi, Taste Masking: A Novel Approach for Bitter and

Obnoxious Drugs, Journal of Pharmaceutical Science Bioscientific Research,
Volume 1, Issue 3: Nov -Dec 2011 Page no.- 136-142.
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 Zelalem Ayenew, Trends in Pharmaceutical Taste Masking Technologies: A
Patent Review, Recent Patents on Drug Delivery & Formulation 2009, 3, Page
no.- 26-39.

 S. T. Birhade, Preparation and Evaluation of Cyclodextrin Based Binary

Systems for Taste Masking, International Journal of Pharmaceutical Sciences and
Drug Research 2010; 2(3): Page no.- 199-203.

 Patidar ashish, A Review On- Recent Advancement In The Development of

Rapid Disintegrating Tablet, International Journal of Life science & Pharma
Research, Vol 1/Issue 1/Oct-Dec 2011, Page no.- 7-15.

 Rajesh Agrawal, Cyclodextrins – A Review on Pharmaceutical Application for

Drug Delivery, International Journal of Pharmaceutical Frontier Research, Jan-
Mar 2012; 2(1), Page no.- 95-112.

 Vijay D. Wagh, Taste Masking Methods and Techniques in Oral

Pharmaceuticals: Current Perspectives, Journal of Pharmacy Research 2009, 2(6),
Page no.- 1049-1054. 5/17/2012 40
 Gupta A. K., Practical Approaches for Taste Masking of Bitter Drug: A
Review, International Journal of Drug Delivery Technology, 2010; 2(2), Page no.-
56-61.

 S. B. Ahire, A Review: Taste Masking Techniques in Pharmaceuticals, An

International Journal of Pharmaceutical Sciences, IC Value – 4.01, Page no.-
1645-1657.

 Vijay A. Agrawal, Taste Abatement Techniques to Inprove Palatability of Oral

Pharmaceuticals: a Review, International Journal of Pharma Research and
Development, 2010/VOV-2/ISSUE-7/SEP/008, Page no.- 1-7.

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 Thank you…
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