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WHAT IS TASTE ?

Four main taste perceptions: salt, sour, bitter, and sweet.

Two other perceptions (umami and trigeminal).

Umami is derived from the presence of glutamate, such as monosodium glutamate, resulting in the fullness sensation.

Trigeminal is the burning sensation derived from such foods as spices and peppers.

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FACTORS AFFECTING THE PERCEPTION OF BITTERNESS

Taste Interactions.

Medium of Presentation.

Viscosity.

Temperature.

Taste Modifiers.

Salivary Status.

Age.

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METHODS OF IMPROVING THE PALATABILITY

Chemical• Complexation• Pro-drug

Physical• Less soluble

derivative• Precipitation• Emulsion• Viscous vehicle

Physiological• Anaesthetic action• Effervescence• Cooling effect

Masking&

Blending

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Techniques Employed

for Taste Masking

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1 -Use of Flavours & Sweeteners

Natural Flavours• Juices - Raspberry• Extracts - Liquorice• Spirits - Lemon & Orange• Syrups - Blackcurrant• Tinctures - Ginger• Aromatic waters - Anise & Cinnamon• Oils - Lemon & Orange

Synthetic Flavours• Alcoholic solutions• Aqueous solutions• Powders

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2 - Use of sweeteners

• • Sucrose, glucose, fructose• • Sorbitol, mannitol, glycerol• • Honey, liquorice

Natural Sweeten

er

• • Saccharin, saccharin sodium• • Aspartame

Artificial sweetene

r• • Intense sweetener• • Sugar free preparation• • Enhance degree of sweetness• • Disadvantage – bitter or metallic

aftertaste

Advantage of

Artificial Sweeten

er

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FDA approved Non-Nutritive Sweeteners

Asparatame

Sucralose

Neotame

Saccharin

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3 - Applying polymers

Coating of drugs using a suitable polymer

offer an excellent method of concealing

the drug from the taste buds.

The coated composition may be

incorporated into much number of

pharmaceutical formulations, including

chewable tablet, effervescent tablets,

powder, and liquid dispersion etc.

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3. 1. Coating Polymers

Eudragit E100, is finding fairly broad

utility in taste-masking drugs when a

rapid release is needed.

Neutral polymers like methacrylate

copolymers, ethyl cellulose or

cellulose acetate butyrate, Eudragit

RS can also provide sufficient time

delay for use in taste-masking.

Water-soluble polymers such as

HPMC may be used to decrease barrier

properties of taste-masking coatings.

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3.2 Meltable Coatings

Hydrogenated

vegetable oils,

Vegetable waxes

Saturated fatty acids

such as stearic acid

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3.3. Coating of Drug Particles

Powders as fine as 50 micron are

fluidized in an expansion chamber by

means of heated, high-velocity air,

and the drug particles are coated with

a coating solution introduced usually

from the top as a spray through a

nozzle.

Taste-masking of Ibuprofen has been

successfully achieved by this

technique to form microcapsules.

Starches, polyvinyl pyrrolidones

(povidone) of various molecular

weights, gelatin, methylcellulose,

hydroxyl methylcellulose,

microcrystalline cellulose and

ethyl cellulose.

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3.4. Camouflage Technology

Polymeric taste masking

process Simple to use Cost effective Colorless Tasteless, taste

masking Sugar free

High drug loading

Dissolves rapidly Non-systemic

absorption of polymer Enhances

stability Used in approved

products

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3.5. Microencapsula

tion Uses various coating agents, such as gelatin, povidone, HEC, EC, bees wax, carnuba wax and shellac.

Bitter-tasting drugs can be first encapsulated to produce free flowing microcapsules, which are then blended with other excipients and compressed into tablets.

Microencapsulation also increases the stability of the drug and release pattern can be modified .

It can be accomplished by a variety of methods, air suspension, coacervation -phase separation, spray drying and congealing, pan coating, solvent evaporation multi-orifice centrifugation techniques.

It has been reported that the bitter taste of paracetamol was completely masked on microencapsulation using cellulose-wax combination.

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3.6. Complexation with ion exchange resins

The adsorption of bitter drugs onto synthetic ion

exchange resins to achieve taste coverage has

been well documented.

Extreme bitterness of quinolones has been

achieved by ion exchange resin such as

methacrylic acid polymer cross linked with

di-vinyl benzene.

Drugs with cationic functionality (e.g. -COOH or Na

/ K salts) DUOLITE™ AP143.

Drugs with anionic functionality (-NH2, HCl salts

etc.) AMBERLITE™ IRP64.

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3.7. Inclusion complex with cyclodextrins

Cyclodextrin is the most widely used complexing agent for inclusion complex formation which is capable of masking the bitter taste of the drug.

By decreasing the amount of drug particles exposed to taste buds there by reducing its perception of bitter taste.

Bitter taste of ibuprofen has been effectively masked by cyclodextrin.

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3.8. Taste Masking by Ionic Interaction

For this technology, two combinations are possible: using an anionic drug and a cationic polymer, or a cationic drug together with an anionic polymer.

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3.10. Pelletization

Taste masking is achieved when the bitter value (short: BV) is decreased three times by the power of ten.BV is determined as the reciprocal drug concentration that tastes slightly unpleasant (according to German Pharmacopeias DAB 10).

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3.11. Molecular Complexes of Drugs

The solubility and absorption of

drugs can be modified by the

formation of molecular complexes.

Lowering drug solubility through

molecular complexation can decrease

the intensity of bitterness.

The bitterness of caffeine was

completely masked by the formation of a

molecular complex of caffeine and

gentisic acid in 1:1 and 1:2 molar

ratios.

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3.12. Solid Dispersions They are dispersions of one or more

active ingredient in an inert carrier or

matrix in solid state, and insoluble or

bland matrices may be used to mask the

taste of bitter drugs.

HPMC, mannitol and ethylcellulose.

Approaches for preparation of solid

dispersion are described below. Melting method: Solvent method: Melting-solvent method:

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3.13. Formation of Salts or Derivatives

In this approach, an attempt is made to

modify the chemical composition of

the drug substance itself, so as to

render it less soluble in saliva and thus

make it less sensitive to the taste buds.

Aspirin tablets can be rendered

tasteless by making magnesium salt of

aspirin.

D-chlorpheniramine maleate is a

taste-masked salt of chlorpheniramine.

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3.14. Use of Amino Acids By combining amino acids or their salts

with bitter drugs, it is possible to

substantially reduce the bitterness.

Some of the preferred amino acids include

sarcosine, alanine, taurine, glutamic

acid, and glycine.

The taste of ampicillin improved

markedly by preparing its granules

with glycine and mixing them with

additional quantity of glycine, sweeteners,

flavors and finally compressing them into

tablets.

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3.15. Taste-masking by Viscosity Modifications

Increasing the viscosity with

thickening agents can lower the

diffusion of bitter substances from

the saliva to the taste buds.

This provides a taste masked liquid

preparation for administration of a

relatively large amount of unpleasant

tasting medicines.

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3.16. Incorporation of drugs into vesicles or liposomes Incorporation of drugs into vesicles or

liposomes is although an ideal technique, yet a challenge to formulate without altering the regulatory status of the product

3.17. Anesthetizing agent Anesthetizing agent like sodium

phenolate, which numb the taste buds sufficiently within 4-5 seconds is helpful in inhibiting the perception of bitter taste of the formulation.

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3.18 Multiple emulsions

Another novel technique employing multiple

emulsions has also been reported. 

By dissolving drug in the inner aqueous

phase of w/o/w emulsion

In one of the method drugs with bitter taste

are combined with nonionic surfactants

to form composites by hydrophobic

interactions resulting in taste masking.

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3.18. Freeze drying process

Various drugs have been taste masked by

zydis technology.

This includes the drugs like lorazepam,

piroxicam, loperamide, ondansantron,

rizatriptan, loratadine, olanzapine,

selegiline etc.

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Oralance ® technology The Oralance ® technology efficiently

hides the taste of the most difficult molecules even formulated in aqueous media

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Evaluation of

Taste Masking Effect

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4.1. Pharmaceutical taste-assessment

requires Trained taste panel and sophisticated interpretation.

E- Tongue

E- Nose

Olfactory Gas Chromatography

In vitro cell Cultures

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4.2. How does e-tongue works ?

The e- tongue mirrors the three levels of biological taste recogination:

The Receptor

level

The Circuitlevel

The Perceptual

level

Probe membranes

Taste buds

Neural transmission

Cognition in the thalamus

Computer and statistical analysis

Transducer

Human Tongue E-tongue

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Key benefit of e- tongue evaluation

1. Help to quantify bitterness of drug

actives when limited basic taste

information is available, especially if the

drug supply is limited.

2. Developing suitable matching bitter

placebos for blinded clinical testing

3. Conduct comparator studies

(Benchmark analysis)

4. Developing optimized taste- masked

formulations.

5. Serving a quality control function for

flavored product and excipient.

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Use of Electronic Nose to Optimize Flavor Profile

Company that commercially produce e-nose : Alpha M.O.S. (DeMotte, IN), AromaScan (Hollis, NH), and Neotronics (Gainesville, GA).

Human nose: 10,000 odor sensors (nonspecific) but can be very sensitive to certain odors.

Signals from human olfactory sensors are transmitted to the brain for processing.

The brain then interprets what the sum of all these signals is describing in terms of odor.

Electronic Nose instruments attempt to do the same with many fewer sensors and a simulated brain consisting of a computer and sophisticated software.

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Use of Cell Cultures & Receptors

Cloning of receptor proteins, individual

receptors or the whole sensory organ

may produce detection systems with similar

function to the human sensory organs.

However, it will be necessary to

deconvolute the signals obtained from

these systems to convert them into terms

typically used to describe our

perception of stimuli.

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Olfactory Gas Chromatographic

Technique Olfactory GC techniques permitted the

division of identified volatiles into odor-active and non-odor-active.

Deal with measurements of volatile release in the mouth by a novel nose sampler and oral vapor GC. These useful tools clarify the effects of breathing, chewing, and

saliva flow on flavor release

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PARTICLES COATING

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Applications of particle coating

Modification of particles to mask flavors, odor & color

Modification of reactivity, solubility and wetting properties

Taste masking with modified release

Separation of incompatibilities

Conversion of liquids to solids

Sustained release

Flowability

Partice size distribution

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Dispersibility

Hydrophilic/Hydrophobic Properties

Electrostatic/Electric/Magnetic/Optical Characteristics

Achieve sphericity

Solid Phase reactivity

Cont…

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Various Particles Coating

Techniques

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Microencapsulation

Versatile for individual particles coating

The type and level of membrane applied is

determined by release rate

requirements, organoleptic features

and the dosage form application.

Microcaps particles can be incorporated

into different dosage forms including fast

melt tablets, sachets, sprinkles and

reconstitutable and temporary

suspensions.

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Spray Drying

Inexpensive methods for coating particles.

Suspension is spray dried

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Spray drying systems

Open spray drying system Closed spray drying system

Semi-closed spray drying systemAseptic spray drying system

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Fluid bed coating techniques

It is used to dry the wet products,

agglomerate particles,

improve flow properties, produce

coated particles for

controlled release or taste masking

Ease of scale up

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Open system CLosed system

Batch fluid bed system

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Bottom spray coater

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Wuster coater :- industry recognized coating for precision application of film coat to particulate material like powder, crystal, granule

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Thin Precision coating technique for fine powders

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Dry Particle coating Equipments

HIGH INTENSITY MACHINES :

Hybridizer Mechanofusion Theta Composer

FLUIDIZATION BASED DEVICES :

Magnetically Assisted Impaction Coating ( MAIC)

Rotating Fluidized Bed coater ( RFBC)

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DRY PARTICLE COATING

Mechanical ForcesDiscrete coating

Continuous coatingHost particle

Guest particle

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Mechanofusion Use high mechanical force between

the fixed arm head and rotating

chamber Wall for embedding guest

particles onto host particles.Scraper

Rotating Chamber

Arm head

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Hybridizer

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Theta ComposerCapacity : 40cc ;

Powder occupied Volume : 20 %

Outside Vessel : 30 rpm ;

Rotor : 500 ~ 3000rpm

Slow revolution of outside vessel: Promotion of favourable bulk mixingHigh speed rotation of inside rotor : high shear stress required for coating.Elliptical Shape:Stress & relaxation

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Rotating Fluidized bed coater

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Vertical Rotating Fluidized bed coater

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Magnetically Assisted Impact Coating

(MAIC)

N-S S-N

AC Power supply

Guest Particle

Host particle

Magnetic particle

Chamber

Collar coil

Oscillatingmagnetic fieldHost

Guest

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1. Michelle Ramlakhan, C.-Y. Wu, Satoru Watano, R.N. Dave, Robert Pfeffer, Dry particle coating using magnetically assisted impaction coatings: modification of surface properties and optimization of system operating parameters, Powder Technology 112 (2000) 137–148.

2. P. Singh, T.K.S. Solanky, R. Mudryy, R. Pfeffer, R.N. Dave, Estimation of coating time in the magnetically assisted impaction coating process, Powder Technology 121 (2–3) (2001) 159–167.

3. Nethersole, Douglas C.; Dudley, Michael A.; Parthasarathy, Mellapalayam 4. R.; United States Patent 4069792

Rodriguez L, Albertini B, Passerini N, Cavallari C, Giovannelli L. Hot air coating technique as a novel method to produce microparticles. Drug Dev Ind Pharm. 2004; 30(9):913-23.

5. Powder Coater’s Manual 1/986. www. biophan - nanotechwire_com - the online resource for nano

technology and research7. www. ventilex.htm8. www. caleva.co.uk9. www. coating place.inc.htm

References

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“ The greatest discovery of our generation is that a human being can alter his life by altering his attitude of mind “

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nks