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#AAPS2017Slide 1
The Science of Taste Perception and Sensory Analysis
13 November 2017
David Tisi
#AAPS2017Slide 2
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
#AAPS2017Slide 3
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.
#AAPS2017Slide 4
OVERVIEW
Anatomy and Physiology of Taste and Smell
Psychophysics
Sensory Analysis
Analytical Measurement Techniques
Affective Measurement Techniques
#AAPS2017Slide 5
OVERVIEW
Anatomy and Physiology of Taste and Smell
Psychophysics
Sensory Analysis
Analytical Measurement Techniques
Affective Measurement Techniques
#AAPS2017Slide 6
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)
#AAPS2017Slide 7
1) Taste (Gustation)
Flavor
Basic Taste
Aroma
Feeling Factors
Texture
#AAPS2017Slide 8
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?
#AAPS2017Slide 9
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
#AAPS2017Slide 10
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
#AAPS2017Slide 11
Two competing theories describe the gustatory perception pathway
mechanism.
“Labeled Line” Model “Across Fiber” Model
Chandrashekar, Nature 2006BitterSaltySweet
SourUmami
#AAPS2017Slide 12
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
#AAPS2017Slide 13
2) Aroma (Olfaction)
Flavor
Basic Taste
Aroma
Feeling Factors
Texture
#AAPS2017Slide 14
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
#AAPS2017Slide 15
Activated olfactory neurons stimulate mitral cells of the brain at
nerve groupings called glomeruli located in the olfactory bulb.
Lynch 2006
#AAPS2017Slide 16
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.
#AAPS2017Slide 17
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
#AAPS2017Slide 18
Coincidentally, perfumers and “flavorists” who artificially concoct
these blends of aromas sometimes work in a perfumer’s “organ”.
#AAPS2017Slide 19
3) Feeling Factors (Chemesthesis)
Flavor
Basic Taste
Aroma
Feeling Factors
Texture
#AAPS2017Slide 20
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
#AAPS2017Slide 21
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)
#AAPS2017Slide 22
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
#AAPS2017Slide 23
4) Texture (Tactile Sensations)
Flavor
Basic Taste
Aroma
Feeling Factors
Texture
#AAPS2017Slide 24
Mastication forms a complicated decision tree with the end goal of
particle size reduction before swallowing.
Lucas 2002
#AAPS2017Slide 25
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:
#AAPS2017Slide 26
Development of preference.
#AAPS2017Slide 27
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
#AAPS2017Slide 28
“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
#AAPS2017Slide 29
OVERVIEW
Anatomy and Physiology of Taste and Smell
Psychophysics
Sensory Analysis
Analytical Measurement Techniques
Affective Measurement Techniques
#AAPS2017Slide 30
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
#AAPS2017Slide 31
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?
??
#AAPS2017Slide 32
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
#AAPS2017Slide 33
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
#AAPS2017Slide 34
Biedler introduced a Michaelis-Menten biometric model for receptor
saturation.
L.M. Beidler(1922-2003)
Lawless 2010
R = (RmaxC)/(K+C)
#AAPS2017Slide 35
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
#AAPS2017Slide 36
OVERVIEW
Anatomy and Physiology of Taste and Smell
Psychophysics
Sensory Analysis
Analytical Measurement Techniques
Affective Measurement Techniques
#AAPS2017Slide 37
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.”
#AAPS2017Slide 38
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.
#AAPS2017Slide 39
OVERVIEW
Anatomy and Physiology of Taste and Smell
Psychophysics
Sensory Analysis
Analytical Measurement Techniques
Affective Measurement Techniques
#AAPS2017Slide 40
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.
#AAPS2017Slide 41
Analytical Sensory Methods
Descriptive Methods are used to guide Product Development
• Questions to be answered:
• 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
#AAPS2017Slide 42
Analytical Sensory Methods
Descriptive Methods are used to guide Product Development
Data:
• Identification and quantification of allperceived flavors.
• Subjects are calibrated to known chemical reference standards.
• Akin to an instrumental output
Illustrative
#AAPS2017Slide 43
Analytical Sensory Methods
Descriptive Methods are used to guide Product Development
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
#AAPS2017Slide 44
Analytical Sensory Methods
Descriptive Methods are used to guide Product Development
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
#AAPS2017Slide 45
OVERVIEW
Anatomy and Physiology of Taste and Smell
Psychophysics
Sensory Analysis
Analytical Measurement Techniques
Affective Measurement Techniques
#AAPS2017Slide 46
Affective Sensory Methods
Preference Testing
#AAPS2017Slide 47
Affective Sensory Methods
Preference Testing is used to Support Launch Decisions
• Questions to be answered:
• “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
#AAPS2017Slide 48
Affective Sensory Methods
Hedonic Testing is used to Support Launch Decisions
• Questions to be answered:
• “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
#AAPS2017Slide 49
Affective Sensory Methods
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
#AAPS2017Slide 50
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
#AAPS2017Slide 51
Expert Methods
• Commodity specific grading scales
• Industry specific quality scores
• Based on preference of 1 assessor (cheesemaker, critic, master distiller) using esoteric language
#AAPS2017Slide 52
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
#AAPS2017Slide 53
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.*
#AAPS2017Slide 56
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.
#AAPS2017Slide 57
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.