the science of taste perception and sensory analysis · pdf fileof formulation flavor is...

#AAPS2017Slide 1

The Science of Taste Perception and Sensory Analysis

13 November 2017

David Tisi

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Session Description and Objectives

• The development of palatable formulations is critically important for medicines intended for the pediatric population. This is reflected by regulations in the United States and European Union that are stimulating research into the development of drug products specifically labeled for pediatric dosing. As the core competencies of the pharmaceutical industry typically involve determining efficacy and safety of drug formulations, the measurement and optimization of formulation flavor is outside the specific expertise of pharmaceutical scientists. This is the converse of the food industry, which strives to develop products that delight the palate because “taste is king”. Accordingly, methodologies employed in food product development may prove useful to consider when developing oral drug products, particularly when those formulations are targeted at children. This session will explore the anatomy and physiology of taste and smell, and review those sensory methods used extensively by the food industry to objectively measure the flavor of products and measure subjective preferences of consumers.

• Provide a basic understanding of:

• The physiology of flavor

perception

• The psychological models

describing human perception

of stimuli intensity

• The sensory analysis

methods used to measure

flavor

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Biography and Contact Information

• David Tisi is the Technical Director at Senopsys LLC

• Mr. Tisi’s career has been spent at the interface of food technology

and pharmaceutical development, applying tools techniques and

approaches from the food industry into pharmaceutical

development.

• Mr. Tisi received a Masters in Food Chemistry from Cornell

University, and has worked in product development for PepsiCo

and Nestle.

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OVERVIEW

Anatomy and Physiology of Taste and Smell

Psychophysics

Sensory Analysis

Analytical Measurement Techniques

Affective Measurement Techniques

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OVERVIEW


Psychophysics

Sensory Analysis



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Flavor – as defined by sensory science is “The sum of the

perceptions from stimulation of the sense ends at the entrance of

the alimentary and respiratory tracts”*

*Amerine et al., 1965

Flavor

Basic Taste(Gustation)

Aroma(Olfaction)

Feeling Factors(Chemesthesis)

Texture(Tactile)

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1) Taste (Gustation)

Flavor

Basic Taste

Aroma

Feeling Factors

Texture

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Taste refers to the perception of 5 agreed-upon chemical

sensations, known as “Basic Tastes”.

Basic Taste Example Stimulus Nutritional Purpose

Sweet Sucrose / Saccharin Energy

Sour Hydronium Ions Ripeness / Decay

Salty Sodium Chloride Ionic Balance

Bitter Caffeine / Many APIs Poison

Umami Peptides / Amino Acids / MSG Energy

• Other proposed tastes:• Metallic?

• Fatty?

• Starchy?

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Tastant molecules are perceived

by taste buds which line the oral

cavity epithelium (particularly

the tongue).

• Each taste bud contains 30-50 taste receptor cells (TRCs).

• TRCs project microvillaeforming a taste pore.

• Receptor active sites are on the surface of microvilli.

• TRCs are epithelial cells, with electrical properties similar to neurons

Taste receptor

cell

Tastepore Microvilli

Nerve fiber

2016 Pearson

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Receptor mechanisms differ by taste type, and upon stimulation fire

an action potential.

A) Sweet, Bitter, Umami• G Protein Receptor (GPCR)

• Complex signal cascade

Chaudhari, JCB 2010

B,C) Sour, Salt• Ion diffusion

• Comparatively more simple

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Two competing theories describe the gustatory perception pathway

mechanism.

“Labeled Line” Model “Across Fiber” Model

Chandrashekar, Nature 2006BitterSaltySweet

SourUmami

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Excited axons stimulate the gustatory cortex of the brain’s insular

lobe via the thalamus.

2016 Pearson

Glossopharyngeal nerve (IX)

Thalamus

Solitary nucleus

(medulla oblongata)

Vagus nerve (X)

Gustatory cortex (insula)

Facial nerve (VII)

Taste

Receptor

Cells

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2) Aroma (Olfaction)

Flavor

Basic Taste

Aroma

Feeling Factors

Texture

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Lynch 2006

Olfactory bulb Cribriform plate

Olfactory epithelium

OrthonasalOlfaction

RetronasalOlfaction

Aromas are perceived by olfactory neurons which pass through the

Cribriform plate (Latin for “perforated”) to the olfactory bulb.

Olfaction may be retronasal or orthonasal in character

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Activated olfactory neurons stimulate mitral cells of the brain at

nerve groupings called glomeruli located in the olfactory bulb.

Lynch 2006

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The perception pathway of olfaction in the brain is fundamentally

different than in all other sensory systems.

• Aroma processing cascades through the limbic system:• Amygdala

• Hypothalamus

• Hippocampus

• Identified in the orbitofrontal cortex

• Olfaction is the only sensory system that does not relay through the thalamus.

• Odors are “felt” first, identified later.

• This is somewhat backwards from other sensory systems, and explains the characteristic emotion and memoryconnections to olfaction.

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An aroma is a blend of molecules which stimulate multiple olfactory

neurons in concert.

• Each olfactory neuron contains one specific olfactory receptor protein selective to one molecule geometry.

• ~400 genes for olfactory receptors

• One or more neurons are stimulated at the same time; much like playing a “chord” on a piano containing hundreds of keys.

Odorant Molecules

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Coincidentally, perfumers and “flavorists” who artificially concoct

these blends of aromas sometimes work in a perfumer’s “organ”.

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3) Feeling Factors (Chemesthesis)

Flavor

Basic Taste

Aroma

Feeling Factors

Texture

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Feeling factors (chemesthesis) are sensations that arise via direct

chemical stimulation of the trigeminal (CN5) nerves.

Example StimuliFeeling Factor

Cooling

Numbing

Bite/Burn

Menthol, Mint

Clove, Parabens

Pepper, Alcohol, CO2

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Transient Receptor Potential (TRP) Ion channels the oral

epithelium stimulate the Trigeminal nerve (CN5), and are

responsible for thermoreception. Some can be triggered chemically.

Ion Channel

Thermal Operation

Chemical Stimulants

TRPV3 Warm (~34-39°C)Cinnemaldehyde (Cinnamon)

Camphor (Thyme/Oregano)

TRPV1 Hot (Pain) (>43°C)Capsaicin (Chili)

Piperine (Black Pepper)

TRPM8 Cool (<25°C)Menthol (Peppermint)

Other Synthetic Chemicals

TRPA1 Cold (Pain) (<18°C)Allicin (Garlic)

Isothiocyanates (Wasabi)

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This chemesthetic process is different from thermal changes (heat

of solution) occurring upon excipient dissolution in the saliva.

-40

-35

-30

-25

-20

-15

-10

-5

0

He

at o

f So

luti

on

(K

cal/

g)

Xylitol-36.6 KCal/g

Sorbitol-26.5 KCal/g

Sucrose-4.3 KCal/g

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4) Texture (Tactile Sensations)

Flavor

Basic Taste

Aroma

Feeling Factors

Texture

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Mastication forms a complicated decision tree with the end goal of

particle size reduction before swallowing.

Lucas 2002

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Texture is the perception of structural changes to a product upon

deformation during oral manipulation.

Class Example Attributes Example Definition

Mechanical

PropertiesHardness, Brittleness

Hardness: The force to attain a

given deformation between the

molars

Geometrical

Properties

Grittiness, Fibrousness,

Coarseness

Grittiness: The degree to which a

sample contains small grainy

particles.

Compositional

Properties

Moistness, Oiliness,

Adhesiveness

Adhesiveness: The force

required to remove a sample from

the hard palate.

Textures may be grouped into three classes:

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Development of preference.

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Children and adults live in the same sensory world – flavor

perception is the same, flavor preference changes during

development.

Attribute Innate Response Learned Response Preference Difference

Basic

Tastes

• Like of Sweet (Energy)

• Dislike Bitter (Poison)

• Neutral to Sour, Salt

• Aversion may be

overcome in adulthood

(e.g. coffee, beer)

• Children prefer higher

intensity sweetness and

sourness compared to

adults

Aromas • No innate response• Aromas introduced by

caregiver

• Children prefer familiar

aromas (e.g., citrus,

berry)

• Aroma palette becomes

more complex with age

Feeling

Factors• Aversion (Hazard/Pain)

• Aversion may be

overcome in adulthood

• Expectations become

more complex with age

Textures • Liquids and thin pastes

• Novel textures may be

introduced as

mastication becomes

more efficient

• Certain children may

actively seek novel

textures

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“Fake News”

• “90% of taste is smell”

• “I have a cold, I can’t taste anything”

• “This smells sour”

• “This tastes bitter”• Maybe or maybe not – 25% of adults call sour solutions

as “bitter”.

* Musselman et. al. 1969** Omahony et. al. 1979

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OVERVIEW


Psychophysics

Sensory Analysis



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One of the cardinal branches of experimental psychology is

psychophysics, the study of the relation between stimulus and

perception.

ΔI / I = k

Ernest Weber (1795-1878)

• The size of the “Just Noticeable Difference” (JND) is proportion (linear) to the stimulus intensity.

• Human sensory sensitivity is relative rather than absolute in nature

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This “Weber fraction” is an index of how well the sensory system

detects changes (Visual, Acoustical, Tactile, Gustatory, Olfactory).

1 Sugar vs. 2 ? 9 vs. 10 ?

10 Dots

20 Dots

Perc

eiv

ed D

iffe

rence

110 Dots

120 Dots

Maybe N

ot?

??

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Gustav Fechner determined that the stimulus/response relationship

was logarithmic in nature.

S = k log I

Gustav Fechner (1801-1887)

Pe

rce

ive

d In

ten

sity

(S)

Physical Stimuli (I) Woulfe 2006

• Perceived intensity (S) is a logarithmic relationship to the physical stimuli (I).

• JND can be used as a basic unit of scales

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Stevens determined that some modalities (perceived viscosity and

electric shock) were log/log in nature, but could not account for

observed data not holding at extremes.

S.S. Stevens(1906-1973)

S=kIn

Lawless 2010

FlavorElements

Brightness

Electric Shock

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Biedler introduced a Michaelis-Menten biometric model for receptor

saturation.

L.M. Beidler(1922-2003)

Lawless 2010

R = (RmaxC)/(K+C)

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The Biedler model may be overlaid with cognitive concepts.

Detection Threshold

Log (Strength)

Perc

eiv

ed

In

ten

sit

y

Str

on

gN

on

e

Recognition Threshold

Sli

gh

tM

od

era

te

Saturation

Linear Response

Source: Senopsys

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OVERVIEW


Psychophysics

Sensory Analysis



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What is Sensory Analysis?

* Stone, H and Sidel, JL. 1993. Sensory Evaluation Practices.

“A scientific discipline used to evoke, measure, analyze and interpret responses to productsperceived by the senses of sight, smell, touch, taste and hearing.”

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In Vitro

Models*

• e-Nose & e-Tongue

• BATA “Rat lick”

• Novel cell model

• Zebra fish

• Amoeba

.

Discover Development Launch

Affective Methods

Used to measure consumer response to products before launch:

‒ Preference

‒ Hedonic

Analytical Methods

Used to measure product attributes and guide development:

‒ Discrimination

‒ Descriptive

In Vivo - Sensory Methods

*Not sensory analysis methods per se; included for illustrative purposes.

Sensory analysis methods can be grouped into two types, which

are used at different stages during product development.

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OVERVIEW


Psychophysics

Sensory Analysis



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Analytical Sensory Methods

Discrimination Methods are used for Quality Control

• Questions to be answered:

• Are these samples different?

• Did a change in excipient suppliers impact the final product flavor?

• Method: Triangle, Duo Trio, or 3-AFC tests (ASTM and ISO)

• Subjects: Trained or Untrained (impact on n), 10-25 participants

• Data: Number of correct responses is compared to the probability of guessing.

Identify the different sample.

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Descriptive Methods are used to guide Product Development


• What are the negative attributes of the API?

• What is the taste threshold concentration of the API?

• Was this new formulation less bitter?

• Method: Flavor Profile, QDA, Spectrum

• ASTM and ISO guidance

• Subjects: Highly trained, 4-12 Participants

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Data:

• Identification and quantification of allperceived flavors.

• Subjects are calibrated to known chemical reference standards.

• Akin to an instrumental output

Illustrative

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Data:

• Spider plots (Compare initial flavor)

• Time/Intensity graphs (Illustrate aftertaste effects)

Beer ABeer BBeer C

0

0.5

1

1.5

2

2.5

3

0 5 10 15 20 25 30

Att

rib

ute

Inte

nsi

ty

Time (Min)

Numbing Phenol Aromatic

Sour Bitter

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Data:

• Determination of taste thresholds

API Concentration

0.0

0.5

1.0

1.5

2.0

2.5

3.0

0 5 10 15 20

Bit

ter

Inte

nsit

y

Minutes in Aftertaste

3.7 mg/mL

6.6 mg/mL

19.3 mg/mL

33.4 mg/mL

57.8 mg/mL

100 mg/mL

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OVERVIEW


Psychophysics

Sensory Analysis



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Affective Sensory Methods

Preference Testing

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Preference Testing is used to Support Launch Decisions


• “Which sample do you prefer?”

• Which formulation should be launched?

• Can a marketing claim be developed?:

• “A greater percentage of children preferred the taste of azithromycin to that of cefpodoxime“

• Method: Paired Preference, Ranking

• ASTM and ISO guidance

• Subjects: Untrained, >25 Participants

• Data: Descriptive statistics with significance treatment

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Hedonic Testing is used to Support Launch Decisions


• “How much do you like this sample?”

• Did a failed discrimination test mean lower preference?

• Quantify preference after a failed discrimination test

• Determine purchase intent (requires existing data)

• Subjects: Untrained, 25-100 Participants

• CPG companies will use many more

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Hedonic Testing is used to Support Launch Decisions

• Methods: Based on Scale (“How much do you like this sample?”)

9-Point Hedonic Scale“Army Quartermaster”

Labeled Affective Magnitude Scale

Facial Hedonic Scale

Unlabeled Line Scale

Like extremely

Like very much

Like moderately

Like slightly

Dislike slightly

Dislike moderately

Dislike very much

Dislike extremely

Neither like nor dislike

Like extremely

Dislike extremely

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Affective Sensory Methods - Considerations

• ISO and ASTM methods provide guidance, not requirements

• Location

• Central Location Testing (CLT)

• Home/Hospital (HUT)

• Demographic

• Caregiver assistance to determine liking

• Number of scale points

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Expert Methods

• Commodity specific grading scales

• Industry specific quality scores

• Based on preference of 1 assessor (cheesemaker, critic, master distiller) using esoteric language

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Two major categories of sensory analysis methods are used to

answer different questions along the continuum from development

to commercialization.

Category Method / Test Question to be Answered Subjects

Analytical

(Develop)

Discrimination“Are these products different

in any way”

Untrained or Trained

• n > 25

Descriptive“In what ways do these

products differ?”

Trained

• n ~4-12

Affective

(Launch)

Preference“Which of these products do

you prefer?”

Untrained

• n > 25

Hedonic“How much do you like this

product?”

Untrained

• n >> 25

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Conclusions

• Taste is not Smell.

• Perceived difference is relative to the stimulus intensity.

• Choose the sensory analysis method based on stage of development.

#AAPS2017Slide 54

Questions

David TisiDirector of Technical Operations, Senopsys LLC

Tel: 781-935-7451Email: [email protected]: www.senopsys.com/taste-masking-blog

#AAPS2017Slide 55

Genetic Differences

* Zhang 2008 ** Miller 1990

• Populations show a normal distribution of taste bud density, which correlates to some difference in stimulus sensitivity.

• High density groups rate:• Sucrose and NaCl as more intense

• Citric acid and quinine as being the same intensity.*

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Genetic Differences

• Multiple genes code for receptor type:• 2 code for umami (TAS1R1 and TAS1R3)• 2 code for sweetness (TAS1R2 and TAS1R3)• 30-40 genes code for bitterness (TAS2R Gene family)

• Salty and sour receptors are comparatively simplistic, and show little deviations between populations

• Some molecules are understood to have a specific non-taster and taster population (PROP / PTC), which may not be predictive a priori.

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Genetic Differences

• There is no “average taster” (or smeller)

• Differences in sensitivity and genetic variation are overcome through enlisting a panel of assessors

• The average response of a group is more valuable than one subset of the population.

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