The document reviews trends in taste masking technologies for pharmaceuticals, focusing on patents from 1997 to 2007. It discusses various methods such as coating, microencapsulation, granulation, and the use of sweeteners to improve the palatability of bitter medications. Additionally, it highlights the challenges of taste masking for different drug formulations and provides insights on the selection of appropriate masking strategies based on the drug's characteristics.

1. Taste Pathway

2. Ventral posterior
medial nucleus of
thalamus
or parietal
cerebral
cortex
(nuclei of tractus solitarius)

3. Epithelial cells
in taste buds
Supporting
cells
Gustatory
receptor cells
Basal cells

4. Papillae
for taste
Vallate
Papillae
Fungiform
Papillae
Foliate
Papillae

5. CLINICAL CONSIDERATIONS
Ageusia: Absence of sense of taste
Dysgeusia: Disturbed sense of taste
Hypogeusia: Diminshed sense of taste
Hypergeusia: increased sense of taste

6. Trends in Pharmaceutical Taste Masking
Technologies: A Patent Review
Z. Ayenew, V. Puri, L. Kumar and A. K. Bansal, Recent Patents on Drug
Delivery & Formulation 2009, 3, 26-39.
Department of Quality Assurance
ISF COLLEGE OF PHARMACY
MOGA – 142001
Presented by:- Saurav Bhandari

7. INTRODUCTION
• The flavor of a substance is attributed to its taste, sight, odor and qualities
such as mouth feel.
• Taste refers to a perception arising from the stimulation of taste buds
present on the surface of the tongue.
• Humans can distinguish among five components of taste:
1.
2.
3.
4.
5.
Sourness
Saltiness
Sweetness
Bitterness
Umami (savory)

8. INTRODUCTION
• The sweet, salty and the sour-taste receptors are concentrated on the tip
and both edges of the tongue.
• Bitter taste is perceived by the receptors at the back of the tongue.
• Umami taste receptors are located all over the tongue.
•
This article focuses on the current trends in the taste masking
technologies summarized from the state of art patents filed in the 10 year
span of 1997 to 2007 in this field.
• It discusses the reported taste masking technologies and the factors
governing the selection of taste masking strategies for a particular drug.

9. CURRENT TRENDS IN TASTE MASKING
TECHNOLOGIES
• The worldwide database of European patent office (http://
ep.espacenet.com) was used to search the taste masking patents and the
patent applications published in the period of year 1997 to 2007.

10. CURRENT TRENDS IN TASTE MASKING
TECHNOLOGIES
• Taste masking technologies are increasingly focussed on aggressively
bitter tasting drugs like
1.
2.
3.
Macrolide anti-biotics
Non-steroidal anti-inflammatory drugs
Peni-cillins
•
Taste masking of water soluble bitter drugs, especially those with a high
dose, is difficult to achieve by using sweeteners alone. As a
consequence, more efficient techniques such as coating,
microencapsulation and granulation have been used in combination with
the sweeteners.

11. CURRENT TRENDS IN TASTE MASKING
TECHNOLOGIES
•
Coating, which accounts for 27% of patents and patent applications, was
the most commonly used technique.
•
An almost equivalent percentage of patents were filed on the flavors and
sweeteners for taste masking.
•
Microencapsulation, granulation technologies, suppressants
potentiators also hold a prominent share of patents in this field.
•
Less commonly used taste masking technologies were viscosity
modifiers, solid dispersions, complexing agents, ion exchange resins, pH
modifiers these hold 5% share of the total taste masking patents.
and

12. TREND ANALYSIS
PERIODS
SWEETENERS
COATING
1997-2000
Prominent
2001-2004
41.6% Increase
133% Increase
2005-2007
No Increase
78.6% Increase

13. TASTE MASKING TECHNOLOGIES

14. COATING
•
Coating is one of the most efficient and commonly used taste masking
technologies.
•
It is classified based on the type of coating material, coating solvent system,
and the number of coating layers.
•
Hydrophobic polymers, lipids, sweeteners and hydrophilic polymers can be
used as coating materials, either alone or in combination, as a single or multilayer coat.
•
Hydrophobic polymers have been popularly used for coating bitter
medicaments to achieve taste masking. However, hydrophilic polymers may
also provide taste masking. For example, rotogranules containing ibuprofen,
polyvinylpyrrolidone, sodium starch glycolate and sodium lauryl sulfate were
coated with hydrophilic polymers such as hydroxyethyl cellulose or a mixture
of hydroxyethyl cellulose and hydroxypropyl methylcellulose to achieve taste
masking.

15. COATING
• Combinations of pH independent water insoluble polymers such as
cellulose ethers, cellulose ester, polyvinyl acetate and water soluble
polymers such as cellulose acetate butyrate, polyvinylpyrollidone,
hydroxyethyl cellulose have been used to attain a balance between the
taste masking and in vitro release.
• This approach may not be effective for the oral liquid dosage forms such
as suspensions due to a gradual loss of taste masking efficiency upon
storage in the liquid form. In such cases, pH independent water insoluble
polymers can be combined with the enteric or reverse enteric polymers to
increase the taste masking efficiency.
• The pH of formulation maintained between 3.5 and 5 by adding a
buffering agent to prevent the dissolution of polymers. This approach can
provide an efficient taste masked suspensions over a long storage time.

16. GRANULATION
• Mixture of bitter medicaments and sweeteners, hydrophobic polymers,
lipids or waxes can be processed by dry, wet and melt granulation
techniques to prepare taste masked oral solid or liquid dosage forms.
• Granulation is a less expensive, rapid operation and an easily scalable
taste masking technology.
• pH dependent and independent water insoluble polymers, especially the
swelling polymers such as MCC and polycarbophil have been employed.
• During granulation, particle coating may remain incomplete. However, a
swelling matrix phenomenon can reduce the overall diffusion of the
bitter active. Thus, swellable polymers can give a better taste masking in
granulation compared to non swellable polymers.

17. SWEETENERS
• Sweeteners are commonly used in combination with other taste masking
technologies. They can be mixed with bitter taste medicaments to
improve the taste of the core material which is prepared for further
coating or may be added to the coating liquid.
• Artificial sweeteners such as sucralose, aspartame and saccharin have
been used in combination with sugar alcohols such as lactitol, maltitol and
sorbitol to decrease the after-taste perception of artificial sweeteners.
Sucralose can be used with physiologically acceptable acids (e.g. citric
acid) to increase the taste masking efficiency of the sweetener.

18. Sweetener(s)
Sucralose and
acids(e.g. citric
acid)
Sucralose
Drug(s)
Acetaminophen,
guaifenesin and
dextromethorphan
hydrobromide
Amino acids(e.g. Lalanine and L-aspartic
acid and other
Amino acids except
arginine), protein
hydrolysates and
proteins
Comments
Citric acid Low pH(2 to 5) and use of
as a sweetener achieves
an unexpected synergy of bitter
taste masking effectiveness
Improved taste without an
unpleasant, bitter/metallic taste or
after-taste of ingestible products

19. MICROENCAPSULATION
• Coating by enteric polymers in combination with water insoluble and
gastrosoluble polymers have been used for masking the unpleasant taste
of medicaments. Combination of water soluble polymer like gelatin, and
water insoluble coating polymer like ethyl-cellulose was used to prepare
taste masked microcapsules by the phase separation method.
• pH independent water insoluble polymers have been used with enteric
polymers, to achieve taste masking by microencapsulation. Buffering
agents are also included in suspending medium to increase taste masking
efficiency of microcapsules in oral suspensions.

20. TASTE SUPPRESSANTS AND POTENTIATORS
• Taste suppressants compete with bitter substances to bind with the Gprotein coupled (GPCR) receptor sites.
• Lipoproteins are universal bitter taste blockers. Study on animal model
showed that lipoproteins composed of phosphatidic acid and β lactoglobulin inhibit the taste nerve responses to the bitter substances
without affecting those due to the sugars, amino acids, salts or acids.
• Mixture of cooling (e.g. eucalyptol) and warming agents (e.g. methyl
salicylate) was used for taste masking of thymol.
• Potentiators increase the perception of the taste of sweeteners and mask
the unpleasant after taste. Potentiators such as thaumatine,
neohesperidine dihydrochalcone(NHDC) and glycyrrhizin can increase the
perception of sodium or calcium saccharinates, saccharin, acesulfame

21. TASTE SUPPRESSANTS AND POTENTIATORS
• The recent trend of use of bitter taste blockers such as hydroxyflavanones,
adenosine monophosphate and gamma-aminobutanoic acid were found
to be effective to achieve the taste masking of bitter drugs.

22. SOLID DISPERSIONS
• Specific interactions between poorly soluble drugs and hydrophilic
polymers can increase the solubility of the drug
Solution of quinolone + the natural hydrophobic polymer shellac
solvent evaporation
Taste masked solid dispersion
This approach usually requires a higher concentration of excipients
compared to other taste masking techniques.
Natural polymers such as shellac and zein
Enteric poly-mers like derivatives of acrylic acid polymers and phthalate are
good choices to develop the taste masked solid dispersions.

23. ION EXCHANGE RESINS
• Ion exchange resins are high molecular weight polymers with cationic and
anionic functional groups.
Resins form insoluble resinates + oppositely charged drugs
Form weak ionic bonding & maintain low concentration of the free
drug in a suspension
After ingestion, the resinate exchange the drug with the counter ion
in gastrointestinal tract
The drug is eluted & get absorbed

24. VISCOSITY ENHANCERS
Viscosity Enhancers
Retard the migration of
dissolved medicament
from the surface of the
solid particle to the
suspending medium
Decrease the contact
between the bitter
medicament and the
taste receptors

25. VISCOSITY ENHANCERS
• Hypromellose was used as a viscosity modifier in taste masked azelastine
suspension consisting of sucralose as the sweetening agent
• Viscosity enhancers included in suspending vehicle to improve the taste
masking efficiency some examples include1. Xanthan gum
2. Microcrystalline cellulose
3. Sodium carboxymethyl cellulose

26. COMPLEX FORMATION
Complex Formation
Cyclodextrins wraps the
bad tasting molecule to
inhibit its interaction
with the taste buds
Interacts with the gatekeeper proteins of the
taste buds
Sweeteners such as acesulfame can form complex with medicaments to
achieve taste masking.

27. pH MODIFIERS
pH Modifying agents
Generate a specific pH microenvironment in aqueous media
Cause in situ precipitation of the bitter drug substance in saliva
Reduce the overall taste sensation for liquid dosage forms like suspension

28. ADSORBATES
Drug + Adsorbate
The drug may be adsorbed or/and entrapped in the matrix of the porous
component (Adsorbate)
Result in a delayed release of the bitter active during the transit through the
oral cavity

29. FACTORS AFFECTING SELECTION OF TASTE
MASKING TECHNOLOGY

30. 1.
2.
3.
4.
5.
6.
Extent of Bitter Taste
Dose of Active Pharmaceuticals
Drug Particle Shape and Size Distribution
Dosage Forms
Drug Solubility
Ionic Characteristics of the Drug

31. EXTENT OF BITTER TASTE
With aggressively bad tasting medicaments even a little exposure is
sufficient to perceive the bad taste.
• Coating is more efficient technology for aggressively bitter drugs even
though coating imperfections, if present, reduce the efficiency of the
technique
• Microencapsulation of potent bitter active agents such as azithromycin is
insufficient to provide taste masking of liquid oral suspensions.
• Viscosity enhancers can complement the taste masking efficiency. Oral
suspension containing viscosity enhancers can mask the objectionable
taste.

32. DOSE OF ACTIVE PHARMACEUTICALS
• Dose of a drug may dictate whether a particular formulation strategy
would be suitable to achieve taste masking
• Low dose palatable pediatric aspirin oral formulation was developed by
adding sweeteners, but the same approach failed to address the problem
of drugs like acetaminophen because of its high dose
• Coating will be the preferred techinique if dose of drug is high

33. DRUG PARTICLE SHAPE AND SIZE DISTRIBUTION
• Core materials with irregular shapes and small particle size lead to poor
taste masking efficiency and varying dissolution of coated particles
Granules of irregular particles are prepared
Coating using internal spacing layer
Coating layer for taste masking to avoid any misperfection in coating

34. DOSAGE FORMS
• Chewable tablets and liquid oral formulations are preferable in case of
large dose drugs for an ease of intake.
• Taste masking technologies such as sweeteners, particulate coating,
microencapsulation and granulation can be employed for chewable
tablets and supported with techno-logies such as viscosity enhancers and
pH modifiers to achieve taste masking in liquid oral formulations
• Microencapsulation of the unpleasant tasting active agent with ethyl
cellulose or a mixture of ethyl cellulose and hydroxypropyl cellulose or
other cellulose derivatives has been used to provide chewable tastemasked dosage forms. However, this approach is having disadvantage that
it also affect release of drug from the formulation. So this is not good for
drugs which are to be used for immediate release.

35. DRUG SOLUBILITY
• Physicochemical properties of the drug play an important role in the
selection of taste masking technology
• Ondansetron has a relatively lower water solubility at higher pH, based on
which a rapidly disintegrating taste masked composition of ondansetron
was formulated by adding an alkalizing agent (sodium bicarbonate) to
reduce the water solubility and also the taste perception
Water Insoluble drug
Water soluble drug
Coat with a Lipid
Formulated in aqueous media, so
Coating with a Lipid is difficult
Coat with polymeric binder

36. IONIC CHARACTERISTICS OF THE DRUG
• Ionic characteristics of drugs govern the selection of ion exchange resin
polymers
• Anionic polymers (e.g. Alginic acid) are good candidates for cationic drugs
like donepezil hydrochloride, and the cationic polymers are choice of
excipients for anionic drugs like sildenafil

37. CURRENT & FUTURE DEVELOPMENTS
• Use of sweeteners is an age old and most popular tool for disguising
bitterness
• The combination of sweeteners with other taste masking technologies
including microencapsulation, particulate coating, bitterness blockers, ion
exchange resins and potentiators is found to be a more efficient strategy.
• Bitter taste blockers which specifically block the bitter taste but not the
pleasant taste of any additive are being explored as universal taste
masking alternatives. Presently, they are limited in number, and most of
them not being GRAS (Generally Regarded As Safe) listed.

38. REFERENCES
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2000. http://www.nature.com/neuro/press_release/nn0200.
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• Yonan J. Umami: Two cookbook authors hope to demystify the littleknown fifth taste. The Boston Globe 2006. http://www.
boston.com/ae/food/articles/2006/03/15/umami/(accessed on May 01,
2008).
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•
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