The Science of Taste Perception and Sensory Analysis

Transcription

1 The Science of Taste Perception and Sensory Analysis 13 November 2017 David Tisi Slide 1

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 Slide 2

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. Slide 3

4 OVERVIEW Anatomy and Physiology of Taste and Smell Psychophysics Sensory Analysis Analytical Measurement Techniques Affective Measurement Techniques Slide 4

5 OVERVIEW Anatomy and Physiology of Taste and Smell Psychophysics Sensory Analysis Analytical Measurement Techniques Affective Measurement Techniques Slide 5

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 * Basic Taste (Gustation) Flavor Aroma (Olfaction) Feeling Factors (Chemesthesis) Texture (Tactile) *Amerine et al., 1965 Slide 6

7 1) Taste (Gustation) Basic Taste Flavor Aroma Feeling Factors Texture Slide 7

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? Slide 8

9 Tastant molecules are perceived by taste buds which line the oral cavity epithelium (particularly the tongue). Taste receptor cell Taste pore Microvilli Each taste bud contains taste receptor cells (TRCs). TRCs project microvillae forming a taste pore. Receptor active sites are on the surface of microvilli. TRCs are epithelial cells, with electrical properties similar to neurons Nerve fiber 2016 Pearson Slide 9

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 B,C) Sour, Salt Ion diffusion Comparatively more simple Chaudhari, JCB 2010 Slide 10

11 Two competing theories describe the gustatory perception pathway mechanism. Labeled Line Model Across Fiber Model Bitter Salty Sweet Sour Umami Slide 11 Chandrashekar, Nature 2006

12 Excited axons stimulate the gustatory cortex of the brain s insular lobe via the thalamus. Gustatory cortex (insula) Thalamus Facial nerve (VII) Solitary nucleus (medulla oblongata) Glossopharyngeal nerve (IX) Vagus nerve (X) 2016 Pearson Taste Receptor Cells Slide 12

13 2) Aroma (Olfaction) Basic Taste Flavor Aroma Feeling Factors Texture Slide 13

14 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 Olfactory bulb Cribriform plate Olfactory epithelium Orthonasal Olfaction Retronasal Olfaction Lynch 2006 Slide 14

15 Activated olfactory neurons stimulate mitral cells of the brain at nerve groupings called glomeruli located in the olfactory bulb. Lynch 2006 Slide 15

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 memory connections to olfaction. Slide 16

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 Slide 17

18 Coincidentally, perfumers and flavorists who artificially concoct these blends of aromas sometimes work in a perfumer s organ. Slide 18

19 3) Feeling Factors (Chemesthesis) Basic Taste Flavor Aroma Feeling Factors Texture Slide 19

20 Feeling factors (chemesthesis) are sensations that arise via direct chemical stimulation of the trigeminal (CN5) nerves. Feeling Factor Example Stimuli Cooling Menthol, Mint Numbing Clove, Parabens Bite/Burn Pepper, Alcohol, CO 2 Slide 20

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 TRPV3 TRPV1 TRPM8 TRPA1 Thermal Operation Warm (~34-39 C) Hot (Pain) (>43 C) Cool (<25 C) Cold (Pain) (<18 C) Chemical Stimulants Cinnemaldehyde (Cinnamon) Camphor (Thyme/Oregano) Capsaicin (Chili) Piperine (Black Pepper) Menthol (Peppermint) Other Synthetic Chemicals Allicin (Garlic) Isothiocyanates (Wasabi) Slide 21

22 Heat of Solution (Kcal/g) This chemesthetic process is different from thermal changes (heat of solution) occurring upon excipient dissolution in the saliva. 0 Xylitol KCal/g Sorbitol KCal/g Sucrose -4.3 KCal/g Slide 22

23 4) Texture (Tactile Sensations) Basic Taste Flavor Aroma Feeling Factors Texture Slide 23

24 Mastication forms a complicated decision tree with the end goal of particle size reduction before swallowing. Lucas 2002 Slide 24

25 Texture is the perception of structural changes to a product upon deformation during oral manipulation. Textures may be grouped into three classes: Class Example Attributes Example Definition Mechanical Properties Geometrical Properties Compositional Properties Hardness, Brittleness Grittiness, Fibrousness, Coarseness Moistness, Oiliness, Adhesiveness Hardness: The force to attain a given deformation between the molars Grittiness: The degree to which a sample contains small grainy particles. Adhesiveness: The force required to remove a sample from the hard palate. Slide 25

26 Development of preference. Slide 26

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 Aromas Like of Sweet (Energy) Dislike Bitter (Poison) Neutral to Sour, Salt No innate response Aversion may be overcome in adulthood (e.g. coffee, beer) Aromas introduced by caregiver Feeling Factors Aversion (Hazard/Pain) Aversion may be overcome in adulthood Textures Liquids and thin pastes Novel textures may be introduced as mastication becomes more efficient Children prefer higher intensity sweetness and sourness compared to adults Children prefer familiar aromas (e.g., citrus, berry) Aroma palette becomes more complex with age Expectations become more complex with age Certain children may actively seek novel textures Slide 27

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 ** Omahony et. al Slide 28

29 OVERVIEW Anatomy and Physiology of Taste and Smell Psychophysics Sensory Analysis Analytical Measurement Techniques Affective Measurement Techniques Slide 29

30 One of the cardinal branches of experimental psychology is psychophysics, the study of the relation between stimulus and perception. The size of the Just Noticeable Difference (JND) is proportion (linear) to the stimulus intensity. ΔI / I = k Ernest Weber ( ) Human sensory sensitivity is relative rather than absolute in nature Slide 30

31 Perceived Difference Maybe Not??? This Weber fraction is an index of how well the sensory system detects changes (Visual, Acoustical, Tactile, Gustatory, Olfactory). 10 Dots 110 Dots 20 Dots 120 Dots 1 Sugar vs. 2? 9 vs. 10? Slide 31

32 Perceived Intensity (S) Gustav Fechner determined that the stimulus/response relationship was logarithmic in nature. Perceived intensity (S) is a logarithmic relationship to the physical stimuli (I). S = k log I JND can be used as a basic unit of scales Gustav Fechner ( ) Slide 32 Physical Stimuli (I) Woulfe 2006

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. Electric Shock Flavor Elements Brightness S.S. Stevens ( ) S=kI n Lawless 2010 Slide 33

34 Biedler introduced a Michaelis-Menten biometric model for receptor saturation. L.M. Beidler ( ) R = (R max C)/(K+C) Lawless 2010 Slide 34

35 None Perceived Intensity Slight Moderate Strong The Biedler model may be overlaid with cognitive concepts. Saturation Linear Response Recognition Threshold Detection Threshold Log (Strength) Slide 35 Source: Senopsys

36 OVERVIEW Anatomy and Physiology of Taste and Smell Psychophysics Sensory Analysis Analytical Measurement Techniques Affective Measurement Techniques Slide 36

37 What is Sensory Analysis? A scientific discipline used to evoke, measure, analyze and interpret responses to products perceived by the senses of sight, smell, touch, taste and hearing. * Stone, H and Sidel, JL Sensory Evaluation Practices. Slide 37

38 Sensory analysis methods can be grouped into two types, which are used at different stages during product development. In Vitro Models* e-nose & e-tongue BATA Rat lick Novel cell model Zebra fish Amoeba In Vivo - Sensory Methods Analytical Methods Used to measure product attributes and guide development: Discrimination Descriptive Affective Methods Used to measure consumer response to products before launch: Preference Hedonic. Discover Development Launch *Not sensory analysis methods per se; included for illustrative purposes. Slide 38

39 OVERVIEW Anatomy and Physiology of Taste and Smell Psychophysics Sensory Analysis Analytical Measurement Techniques Affective Measurement Techniques Slide 39

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) Identify the different sample. Subjects: Trained or Untrained (impact on n), participants Data: Number of correct responses is compared to the probability of guessing. Slide 40

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 Slide 41

42 Analytical Sensory Methods Descriptive Methods are used to guide Product Development Data: Identification and quantification of all perceived flavors. Subjects are calibrated to known chemical reference standards. Akin to an instrumental output Illustrative Slide 42

43 Attribute Intensity Analytical Sensory Methods Descriptive Methods are used to guide Product Development Data: Spider plots (Compare initial flavor) Time/Intensity graphs (Illustrate aftertaste effects) Time (Min) Beer A Beer B Beer C Numbing Sour Phenol Aromatic Bitter Slide 43

44 Bitter Intensity Analytical Sensory Methods Descriptive Methods are used to guide Product Development Data: Determination of taste thresholds API Concentration 3.7 mg/ml 6.6 mg/ml 19.3 mg/ml 33.4 mg/ml 57.8 mg/ml 100 mg/ml Minutes in Aftertaste Slide 44

45 OVERVIEW Anatomy and Physiology of Taste and Smell Psychophysics Sensory Analysis Analytical Measurement Techniques Affective Measurement Techniques Slide 45

46 Affective Sensory Methods Preference Testing Slide 46

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 Slide 47

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, Participants CPG companies will use many more Slide 48

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 Like extremely Like very much Like moderately Like slightly Neither like nor dislike Dislike slightly Dislike moderately Dislike very much Labeled Affective Magnitude Scale Unlabeled Line Scale Like extremely Facial Hedonic Scale Dislike extremely Dislike extremely Slide 49

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 Slide 50

51 Expert Methods Commodity specific grading scales Industry specific quality scores Based on preference of 1 assessor (cheesemaker, critic, master distiller) using esoteric language Slide 51

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 Descriptive Are these products different in any way In what ways do these products differ? Untrained or Trained n > 25 Trained n ~4-12 Affective (Launch) Preference Hedonic Which of these products do you prefer? How much do you like this product? Untrained n > 25 Untrained n >> 25 Slide 52

53 Conclusions Taste is not Smell. Perceived difference is relative to the stimulus intensity. Choose the sensory analysis method based on stage of development. Slide 53

54 Questions David Tisi Director of Technical Operations, Senopsys LLC Tel: Blog: Slide 54

55 Genetic Differences 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. * * Zhang 2008 ** Miller 1990 Slide 55

56 Genetic Differences Multiple genes code for receptor type: 2 code for umami (TAS1R1 and TAS1R3) 2 code for sweetness (TAS1R2 and TAS1R3) 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. Slide 56

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. Slide 57