taste masking approaches & taste evaluation is include in this

1. A
Seminar on
Taste Masking Methods in
Pharmaceutical Formulations
Presented by
Sagar B. Thoke
M. Pharm IInd Semester
[Dept. of Pharmaceutics]
Guided by
Prof . Y. P. Sharma
S.N.D. College of Pharmacy, Babhulgaon.

2. Introduction
 Introduction
 Factors Affecting Selection of Taste Masking Technology
 Factors Consideration During The Taste-Masking Formulation
Process
 Ideal Characteristics of Taste Masking Process & Formulation
 Taste Masking Approaches
 Evaluation Techniques
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3. Introduction
 Need to Formulate Taste Masked Oral formulations.
 Children, older persons-
 Trouble swallowing tablets or capsules
 Prefer liquid or sublingual/ Chewable solid
form dosage form
 Undesirable taste-
 Important formulation problems in case of Oral formulation
 Patient compliance
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4. Anatomy & Physiology of Tongue
 Vasculature
 Lingual artery
 Jugular vein
 Nerve supply
 Facial nerve CN VII
 Glossopharyngeal nerve CN IX
 Musculature Fig. Physiology of Taste Bud
 Intrinsic
 Extrinsic
 Tongue physiology
 Taste buds (taste cells)
 Sense different tastes 4
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5.  Four fundamental sensations of taste
 Sweet and salty, mainly at the tip
 Sour, at the sides
 Bitter, at the back
 fifth is Umami (2002)
 Taste Signaling Pathways Fig. Taste Points in Tongue
1. Drug (tastant) binds with G-PCR in the cells
2. triggering the release the release of G-Protein (Gustducin)
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6. Taste Blocking Mechanism
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7. Factors Affecting Selection of Taste Masking
Technology
 Conventional taste masking techniques alone are often
inadequate in masking the taste of highly bitter drugs such as
quinine, celecoxib.
 Coating imperfections, reduce the efficiency of the technique.
 Microencapsulation of potent bitter azithromycin is insufficient
to provide taste masking of liquid oral suspensions.
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8. Factors Consideration During The Taste-Masking
Formulation Process
1. Extent of the bitter taste of the API & Required dose load.
2. Drug particulate shape and size distribution.
3. Drug solubility and ionic characteristics.
4. Required disintegration and dissolution rate of the finished
product.
5. Desired bioavailability & release profile.
6. Required dosage form.
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9. Ideal Characteristics of Taste Masking Process & Formulation
 It should
1. Involve least number of equipments and processing steps.
2. Effectively mask taste with as few excipients which are
economically and easily available.
3. No adverse effect on drug bioavailability.
4. Least manufacturing cost.
5. Can be carried out at room temperature.
6. Require excipients that have high margin of safety.
7. Rapid and easy to prepare. 9
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10. Taste Masking Approaches
 Two approaches are commonly utilized
1. By reducing the solubility of drug in the pH of saliva
(5.6 - 6.8).
2. By altering the affinity and nature of drug which will
. interact with the taste receptor.
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11. Taste Masking Technologies
 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%.
Fig. Geographical distribution of taste masking patents &
patent application filed in the period of year 1997 to 2007. 11
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12. Fig. Taste masking technology filed in the period of
year 1997 to 2007.
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13. Fig. Taste Masking Technologies uses in liquid and solid dosage forms
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14. 1. Taste Masking with Sweeteners and Flavor's
 Flavors
 Natural Flavors-
Juices – Raspberry, Extracts – Liquorices, Tinctures – Ginger,
Spirits - Lemon & Orange, Syrups – Blackcurrant,
Aromatic waters - Anise & Cinnamon, Aromatic Oils –
Peppermint & Lemon.
 Synthetic Flavors-
Alcoholic solutions, aqueous solutions, Powders.
 Sweeteners
 Complement flavors associated with sweetness
 Soothing effect on the membranes of the throat
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15. Sweeteners used for taste masking
Natural Artificial Nutritive Non- Polyols Novel
Nutritive
Sucrose, Saccharin, Sucrose, Aspartam, Mannitol, Trehalose,
Glucose, Saccharin Fructose, Sucralose, Sorbitol, Tagatose.
Fructose, Sodium, Glucose Neotame, Xylitol,
Sorbitol, Aspartame Saccharine Erythritol,
Mannitol, Maltitol
Honey,
Glycerol,
Liquorice 14
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16. 2. Polymer Coating of Drug
 Coating acts as a physical barrier to the drug particles, by
minimizing interaction between the drug and taste buds.
 Powders (50 mm) is fluidized by
heated, high-velocity air, and the
drug particles are coated with a
coating solution introduced from
the top as a spray through a
nozzle.
 Nontoxic polymer that is
insoluble at pH 7.4 and soluble
at acidic pH are used.
 chewable tablet of crystalline
ibuprofen and methacrylic acid
Fig. Coating process copolymer coating. 16
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17. 3. Formation of Inclusion Complexes
 Complexation of guest molecule with host form a stable complex.
1. Decreasing its oral solubility or
2. Decreasing the amount of drug particles exposed to taste buds.
 most suitable only for low dose drugs.
 β-CD cyclic oligosaccharide obtained from starch.
Fig. Scanning electron micrograph of uncoated (bitter) and
coated (taste masked) paracetamol particles. 17
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18. 4. Ion Exchange Resin Complexes (IER)
 IERs- high mole. weight polymers with cationic and anionic
functional groups.
 Most drugs possess ionic sites in their molecule.
 Drug-resin complex does not dissociate at salivary pH conditions.
 Classification
 Strong cation exchanger- sulphuric acid sites
 Weak cation exchanger- carboxylic acid moieties
 Strong anion exchanger- quaternary amine ionic sites
 Weak anion exchanger- predominantly tertiary amine substituents
e.g. Indion 204, 234, 244, 254; Tulsion T-335, T- 339, T-334;
Amberlite IRC 50, IRP 69, IRP 88, IR 120; Dowex 50.
 Not used- Amberlite IR400; Amberlite IR4B; Dowex 1;
Indion 454; Duolite AP143. 18
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19. 5. Solid Dispersion
 One or more active ingredients Dispersed in an inert carrier or
matrix at solid state.
 Carriers used- povidone, PEG, HPMC, urea, mannitol and
ethylcellulose.
 Methods of Preparation
 Melting method
 Solvent method
 Melting solvent method
Dimenhydrinate with polyvinyl acetate phthalate solid dispersion .
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20. 6. Microencapsulation
 Thin coating to small particles of solids, droplets of liquids and
dispersions.
 Reduce its solubility in saliva &
 Act as physical barrier between drug and taste buds
 Coating agents e.g.
• Gelatin, povidone, hydroxyethyl cellulose, ethyl cellulose,
bees wax, carnuba wax acrylics and shellac.
• water insoluble polymers- cellulose ethers, cellulose
ester, polyvinyl acetate and
• water soluble polymers- cellulose acetate
butyrate, PVP, hydroxyethyl cellulose.
Clarithromycin with combination of gelatine and acrylic resins
(Eudragit L-100, Eudragit S-100 & E-100). 20
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21. 7. Multiple Emulsions
 API entrapped in internal phase of w/o/w or o/w/o emulsion.
w/o/w or o/w/o emulsion of chloroquine phosphate.
8. Development of Liposome
 Liposomes- simple microscopic vesicles in which aqueous
volume (drug or biological agent) is entirely closed by a
membrane composed of lipid molecules.
 lipid bilayers mainly composed of natural or synthetic
phospholipids.
e.g. phosphatidic acid, phosphatidylinositol, soy lecithin.
Chloroquine phosphate in HEPES (N-2-hydroxyetylpiperzine-N’-
2- ethane sulfonic acid) buffer was masked at pH 7.2. by
incorporating into egg phosphatidyl choline. 21
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22. 9. Prodrug Approach
 Chemically modified inert drug precursor upon biotrans-
formation liberates the pharmacologically active parent
compound.
 changing the molecular configuration of the parent molecule
 taste receptor‐substrate adsorption constant may be modified.
Increase or decrease the aqueous solubility, mask bitterness,
increase lipophilicity, improve absorption, decrease local side
effects, and alter membrane permeability of the parent molecule.
Examples of Prodrugs with improved taste
Parent Drug Prodrug
Erythromycin Erythromycin Propionate
Clindamycin Clindamycin palmitate ester
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Chloramphenicol Chloramphenicol palmitate ester 7/16/2012

23. 10. Taste Masking by Adsorption
 Adsorbate of Drug are less saliva soluble versions of drugs.
 Solution of the drug mix with an insoluble powder that will
absorb the drug, removing the solvent, dry it.
e.g. veegum, bentonite, silica gel and silicates.
Loperamide and phenyl propanolamine Suspension-
adsorbed on magnesium aluminium silicates (Veegum F).
11. Taste Masking with Lipophilic Vehicles like Lipids
and Lecithins
 Oils, surfactants, polyalcohols, and lipids effectively increase the
viscosity in the mouth and coat the taste buds.
Talampicillin HCl- Magnesium aluminum silicate with soybean
lecithin. 23
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24. 12. Taste Suppressants and Potentiators
 Suppressants (bitter taste blockers) compete with bitter
substances to bind with the G-protein coupled (GPCR) receptor
sites.
 Not affecting taste due to the sugars, amino acids, salts or
acids.
 Bitter substances (hydrophobic) contributes greatly to their
binding and inter-action with the receptor sites.
• Lipoproteins (phosphatidic acid and β-lactoglobulin)
• adenosine monophosphate
• Phospholipid (BMI-60)
• hydroxyl flavanones & γ-aminobutanoic acid
 Mixture of cooling (e.g. eucalyptol) and warming agents (e.g.
methyl salicylate) was used for taste masking of thymol. 24
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25.  Potentiators increase the perception of the taste of sweeteners.
• thaumatine,
• neohesperidine dihydrochalcone (NHDC) and
• glycyrrhizin
Increase the perception of sodium or calcium
saccharinates, saccharin, aspartyl-phenyl-alanine, cyclamates.
 Desensitizing agents desensitize the taste buds by interfering
with taste transduction.
• phenols
• sodium phenolates
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26. 13. Taste masking by gelation
 Water insoluble gelation on the surface of tablet containing
bitter drug .
 Sodium alginate- form water insoluble gelation in presence of
bivalentmetal ions.
 In presence of saliva, sodium alginate react with bivalent
calcium and form water insoluble gel and thus taste masking
achieved
Amiprolose hydrochloride tablet undercoat of sodium alginate
and overcoat of calcium gluconate.
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27. 14. Formation of salt and derivative
 Salt formation decreasing the solubility of drug (less soluble in
saliva).
• N, N- dibenzyl ethylenediamine diacetate salts or
• N, N bis (deyhdroabiety) ethylene diamine salts is tasteless.
Ibuprofen water-soluble salts using alkaline metal bicarbonate
(sodium bicarbonate).
Aspirin tablets with magnesium salt of aspirin.
Sodium salts- sodium chloride, sodium acetate, sodium
gluconate
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28. 15. Use of Amino Acids and Protein Hydrolysates
 Amino acids or their salts with bitter drugs.
• sarcosine,
• alanine,
• taurine,
• glutamic acid, and
• glycine.
Ampicillin taste improved by its granules with glycine and
additional quantity of glycine, sweeteners, flavors at final
compression step.
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29. 16. Miscellaneous
a) By effervescent agents
It comprises
 chewing gum base
 an orally administrable medicament
 Taste masking generator of carbon dioxide
 optionally a taste bud desensitizing composition e.g. oral
anaesthetics (benzocaine and spilanthol) and
 other non active material, (sweeteners, flavours, and fillers).
Fentanyl and prochlorperazine effervescent tablets for
buccal, sublingual, and gingival absorption.
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30. b) Rheological modification
 Rheological modifier (gums or carbohydrates)-
lower the diffusion of bitter substances from the saliva.
 For administration of liquid preparation.
High viscosity induced by thickening agents
• PEG and
• sodium CMC
Acetaminophen suspension using xanthan gum (0.1‐0.2%) and
microcrystalline cellulose (0.6‐1%).
Mirtazapine (antidepressant) aqueous suspension using methonine
(stabilizer) and maltitol (thickening agent).
 Terbutaline cough syrups given in doses of 4mg/5ml.
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31. c) Continuous multipurpose melt (CMT) technology
 Continuous granulation and coating of API.
d) Wet Spherical Agglomeration (WSA)
 Microencapsulation process combined with wet spherical
agglomeration (WSA).
E.g. Enoxacin taste masking.
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32. e) Freeze Drying Process
 Used to develop FDT.
 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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33. Evaluation Techniques
 Taste masking efficiency as
 Quality control parameter and
 Determining the rate of release of drug from taste-masked
complex.
 Asses by
 in vivo and
 in vitro.
 To quantitatively evaluate taste sensation, following methods
have been reported
a. Human Panel testing (human subjects)
b. Multichannel taste sensor/ magic tongue
c. Spectrophotometric evaluation/ D30’s value 33
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34. In vivo Evaluation
a. Human Panel testing (human subjects)
5‐10 healthy volunteers with organoleptic sense.
Taste evaluation using reference solutions ranging from
tasteless to very bitter.
Place the dosage form in mouth for 10 seconds.
 Demands large panels and elaborate analysis.
 raises safety and scheduling issues.
 time consuming and expensive.
Two sensory analysis methods used-
 Flavor Profile and
 Profile Attribute Analysis
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35. Bitterness recorded against pure drug using a numerical scale.
seven point scale
1 = no bitterness,
2 = very slight bitterness,
3 = slight bitterness,
4 = slight to moderate bitterness,
5 = moderate bitterness,
6 = moderate to strong bitterness, and
7 = strong bitterness.
untrained taster would perceive an objectionable and/or
noticeable bitterness if the bitterness score is greater than or
equal to 3.
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36. In vitro Evaluation
b. Multichannel Taste Sensor / Magic tongue
automated taste sensing device to detect the magnitude of
bitterness.
“E-Tongue” electronic sensor array technology 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).
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37.  Seven (7) sensors designated by Alpha MOS
ZZ, AB, BA, BB, CA, DA, and JE.
 chemically modified sensors- field effect transistors (Chem
FET), similar to an ion selective FET but are coated with a
proprietary coating/membrane.
 Ag/AgCl reference electrode
 probes consist of a silicon transistor with proprietary organic
coatings.
 measurement done potentiometrically.
 taste profile and statistical software interprets the sensor data
into taste patterns.
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38.  Reference electrode and sensors are dipped in a beaker
containing a test solution for 120 seconds.
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39. 42
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40. Click 2 times on the below image
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41. c. Spectrophotometric Method
known quantity of formulation mixed with 10 ml of distilled
water in 10 ml syringe by revolving the syringe, end to end;
five times in 30 seconds.
filtered through a membrane filter & 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.
Sparfloxacin granules, with threshold concentration being
100μg/ml.
Generally the taste evaluation involves
 objective or analytical method and
 subjective or hedonic method 44
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42. Conclusion
Taste masking of bitter drugs has been a challenge to the scientist.
There are numbers of technologies available, which effectively
mask the objectionable taste of drugs. Selection of technology
depends upon the bitterness of drugs and their compatibility with
taste masking agents that does not affect the bioavailability of
drug. With application of these techniques and proper evaluation
of taste masking effect one can improve product preference to a
large extent. Moreover, the development of taste masking
methodology requires great technical skill, and the need for
massive experimentation. 45
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43. References
1) Gupta A. K., Practical Approaches for Taste Masking of Bitter Drug: A Review,
International Journal of Drug Delivery Technology (April-June 2010), Vol. 2, Issue 2,
Page no.- 56-61.
2) S. B. Ahire, A Review: Taste Masking Techniques in Pharmaceuticals, An International
Journal of Pharmaceutical Sciences (2011), Page no.- 1645-1657.
3) Aditi Tripathi, Taste Masking: A Novel Approach for Bitter and Obnoxious Drugs,
Journal of Pharmaceutical Science and Bioscientific research (Nov-Dec 2011), Vol. 1,
Issue 3, Page no.- 136-142.
4) Vijay D. Wagh, Taste Masking Methods and Techniques in Oral Pharmaceuticals:
Current Perspectives, Journal of Pharmacy Research (2009), Vol. 2, Issue 6, Page no.-
1049-1054.
5) Vijay A. Agrawal, Taste Abatement Techniques to Inprove Palatability of Oral
Pharmaceuticals: A Review, International Journal of Pharma Research and Development
(Sep. 2010), Vol. 2, Issue 7, Page no.- 1-10. 46
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44. 6) Vinod M. Sonawane, An Update of Taste Masking Methods and Evaluation
Techniques, Scholars Research Library, Der Pharmacia Lettre (2010), Vol. 2, Issue 6,
Page no.- 1-15.
7) Sidharth Puri, Taste Masking: A Novel Approch For Bitter And Obnoxious Drugs,
International Journal of Biopharmaceutical & Toxicological Research (May 2011), Vol.
1, Issue 1, Page no.- 47-56.
8) J.K. Lorenz et al., Evaluation of a Taste Sensor Instrument (electronic tongue) for Use
In Formulation Development, International Journal of Pharmaceutics (2009), Page no.-
65–72.
9) K Gowthamarajan, Taste-Masking Technologies for Bitter Drugs, General Article
Resonance (December 2004), Page no.- 25-32.
10) Arvind K. Bansal, Trends in Pharmaceutical Taste Masking Technologies: A Patent
Review, Recent Patents on Drug Delivery & Formulation (2009), 3, Page no.- 26-39.
47
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45. 11) A. M. Suthar, Ion Exchange Resin As An Imposing Method For Taste Masking: a
Review, An International Journal of Pharmaceutical Sciences (2010), Vol-1, Issue-2, Page
no.- 6-11.
12) Sanjay Daharwal, Taste Masking Method for Bitter Drug and Tasteless Dispersible
Tablet: An Overview, Page no.- 1-9.
13) Rajesh Agrawal, Cyclodextrins – A Review on Pharmaceutical Application for Drug
Delivery, International Journal of Pharmaceutical Frontier Research (Jan-Mar 2012), Vol.
2, Issue 1, Page no.- 95-112.
14) K.P. Sampath Kumar, Taste Masked Suspension, www.thepharmajournal.com
(2012), Vol. 1 No. 2, Page no.- 1-6.
15) S. T. Birhade, Preparation and Evaluation of Cyclodextrin Based Binary Systems for
Taste Masking, International Journal of Pharmaceutical Sciences and Drug Research
(2010), Vol. 2, Issue 3, Page no.- 199-203.
16) Inderbir SINGH, Scientific Review Ion Exchange Resins: Drug Delivery and
Therapeutic Applications, FABAD J. Pharm. Sci. (2007), 32, Page no.- 91-100. 48
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46. Thank You…!
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