About medicine as a bitter preparation, what is covered here is only the question of taste. How to measure how bitter something is, what to use as the yardstick for that, how far the job of standing in for the tongue can be handed to a machine, and how to hide bitterness — four places are walked through here, only as far as the sources themselves describe. This is a story about design: how the sensation of bitterness is handled from the side of the person taking the medicine — not a story about what happens afterward.
What this page establishes
The definition of the word for a medicine's 「飲みやすさ」 (in translation: "ease of taking") — palatability — is confirmed in the text of regulatory guidelines.
Solutions of quinine hydrochloride and quinine sulfate are confirmed to be used across multiple fields as a reference substance for grading bitterness.
The electronic tongue's statistical models are known to reproduce human bitterness ratings well when comparing drugs of similar chemical character, but the ranking breaks down once drugs of different character are mixed together for comparison.
For quinine hydrochloride, the detection threshold should in principle be lower than the recognition threshold, but in actual measurements the detection threshold instead comes out higher, and the reason for this has not yet been established.
The Words That Measure 「飲める」 (in translation: "can be taken")
A European guideline calls the overall reception of a medicine — with respect to smell, taste, aftertaste, texture, and the like — by a single word: 「パラタビリティ」 (in translation: "palatability"). It states that information on the active substance's own reception should be obtained at an early stage, and that, for pediatric formulations, unless otherwise justified, palatability should be satisfactory on its own — without being mixed into food or drink.
palatability (medicinal product) must be characterised and justified in EU paediatric dossiers: Information on the palatability of the active substance should be obtained early, for example from a dedicated adult panel or from the literature. Unless otherwise justified, the palatability of a pediatric formulation should be satisfactory on its own -- without being mixed into food or drink.contextual
Scope: European Union. The Palatability section of EMA/CHMP/QWP/805880/2012 Rev. 2 (a guideline effective 2014-02-15)
Note: A requirement in the application dossier, not a sensory measurement. The same guideline warns that a pediatric formulation must not resemble candy, because this is known to increase accidental poisoning.
This guideline defines palatability as the overall reception of a (mostly oral) medicinal product with respect to smell, taste, aftertaste, and texture, and requires that information on the active substance's palatability be obtained early (for example, from a dedicated adult panel or from the literature). It states that, unless otherwise justified, the palatability of a pediatric formulation should be satisfactory on its own, that is, met without being mixed into food or drink. It also states that a pediatric formulation must not become too attractive to children (must not resemble candy), and that this is known to raise the rate of accidental poisoning.
Limitations: A regulatory expectation, not an empirical finding. The guideline gives no acceptance criteria, no standard method for palatability testing, and no threshold.
Show dataconcept-palatability —must_be_characterised_and_justified_in_eu_paediatric_dossiers→ "Information on the palatability of the active substance should be obtained early, for example from a dedicated adult panel or from the literature. Unless otherwise justified, the palatability of a pediatric formulation should be satisfactory on its own -- without being mixed into food or drink."
WHO and EMA both position this reception as bearing on how easy a medicine is to keep taking. Both list ease of swallowing, together with taste, at the top of the product characteristics that determine palatability. In a separate survey of children, among those who reported having been reluctant to take a medicine, a high proportion cited taste or flavor as the reason.
palatability (medicinal product) is stated in WHO and EMA documents to materially affect Patient acceptability, and, through it, adherence for oral pediatric medicinescontextual
Scope: Section 3.2 of WHO TRS 970 Annex 5 and Section 10 of EMA/CHMP/QWP/805880/2012 Rev. 2. In both cases, a position statement within a guidance document that reports no effect size
Note: This claim concerns what the 2 official documents themselves state. Neither document quantifies taste's contribution to non-adherence. See the limited evidence from Mennella 2015.
The guideline states that patient acceptability is likely to have a significant impact on patient adherence and, in turn, on the safety and efficacy of the medicine, and lists palatability and ease of swallowing at the top of the product characteristics that determine acceptability.
Limitations: This is expressed as a likelihood ('is likely to have'); the guideline presents no supporting data and no effect size.
This annex defines palatability as the overall acceptance of the taste, flavor, smell, dose volume or size, and texture of a medicine that is taken orally or swallowed, and states that palatability can be decisive for adherence, and that the active substance's palatability can influence the choice of dosage form and its design (which may include taste-masking components).
Limitations: 'Can be decisive' is a qualitative position statement; this annex cites no adherence studies and reports no effect size.
Context: The annex states that children's sensory systems for detecting taste, smell, and chemical irritants are sufficiently developed, that they appear to prefer sweeter tastes than adults, and that the goal of taste masking need not be a delicious medicine -- a taste acceptable in as many countries as possible, with cultural differences taken into account, is sufficient.
Limitations: A statement within a points-to-consider document. The statement about sweetness preference cites only one supporting reference, which has not been read here.
Context: Among 153 responding children aged 3-10, 89 (58.2%) reported experience of refusing medication, and among the 86 who gave a reason, 84.9% (73/86) cited taste or flavor. Swallowing difficulty or throat catching accounted for 8.1% (7/86).
Limitations: These are self-reported reasons for past refusal. The sample is not representative of the population, and medication adherence itself was not measured.
Limits: The authors state that it is unknown how many instances of suboptimal medication use are attributable to a medicine's bad taste alone, and that prospective research is needed to understand the role of individual differences in the acceptance of individual medicines' taste.
Limitations: The quantitative link between palatability and adherence asserted by WHO and EMA has therefore not been established by measurement in the literature read here.
Show dataconcept-palatability —is_stated_by_who_and_ema_to_materially_affect→ "Patient acceptability, and, through it, adherence for oral pediatric medicines"
The Yardstick for Bitterness — Quinine as the Standard
When putting the strength of bitterness into words, research repeatedly calls on one particular compound. In human taste tests, solutions of quinine hydrochloride have been used as the yardstick for grading bitterness.
Scope: Quinine hydrochloride solution in human taste tests
Note: Intensity varies with concentration and mixture context.
Verbatim: "The standard quinine hydrochloride concentrations used were 0.01, 0.03, 0.10, 0.30, and 1.00 mM." The corresponding bitterness scores were defined as 0, 1, 2, 3, and 4 respectively. Volunteer subjects (n = 11) memorized these standard solutions before testing. The 0.1 mM concentration was used as the control solution in the suppression experiment. Quinine hydrochloride was explicitly used as the bitterness standard in this study.
Limitations: 11 panelists. This design measures relative bitterness against a scale that references quinine itself; it establishes the graded bitterness of quinine at 0.01-1.00 mM in solution but gives neither an absolute threshold nor data in a food matrix.
Its standing as a yardstick is not supported by a single receptor alone. In screens using heterologous expression systems, quinine has been confirmed to act as an agonist at multiple bitter-receptor subtypes.
Scope: A heterologous-expression screen curated by IUPHAR/BPS GtoPdb (25 hTAS2R x 104 compounds)
Note: Read at the level of a curated database only, from a single primary study. Meyerhof 2010's full text/supplement (paywalled) is reported to characterize a broader set of quinine receptors, but this is not claimed here.
GtoPdb lists quinine as an Agonist of human TAS2R14, with assayDescription giving Threshold=10 uM and citing Meyerhof 2010 (PMID 20022913).
Limitations: Curation-level evidence. The primary full text could not be read in this survey. GtoPdb lists quinine only against TAS2R14 and TAS2R40, which appears to be a curated subset of the primary data.
An experiment in a separate cultured-cell system also shows that quinine changes how the receptor itself appears at the cell surface. Cell-surface expression changed for multiple T2R receptor subtypes, meaning this compound is involved in how the taste-receptor window itself opens.
quinine affects the cell-surface expression of T2R4, T2R7, T2R10, T2R39, and T2R46 in the cell system studiedpreliminary
Scope: A molecular and pharmacological experiment in a cultured-cell system
Note: Pharmacochaperone activity is distinct from perceived bitterness intensity. Note that 「活性化9受容体」 (in translation: "9 activated receptors") is a cited prior finding, while 「細胞表面発現（シャペロン様）増は5受容体」 (in translation: "increased cell-surface expression [chaperone-like] in 5 receptors") is this paper's own measurement -- these are distinct quantities (confirmed against the full text).
Verbatim: 'Along with T2R4, quinine was reported to activate T2R7, T2R10, T2R14, T2R39, T2R40, T2R43, T2R44 and T2R46' -- 9 receptors in total. This study's own result, verbatim: 'Significant increase in the cell surface expression of T2R4, T2R7, T2R10, T2R39 and T2R46 was observed upon quinine treatment. No significant change in expression of T2R14, T2R40, T2R43 and T2R44 was observed.' Cell-surface expression of T2R4 roughly doubled. Quinine was used at 1 mM, corresponding to the EC50 for T2R4, and pretreatment desensitized the subsequent quinine calcium response, verbatim: 'to 35 +/- 5% (equivalent to 60% +/- 5.2% desensitization).'
Limitations: The list of 9 activated receptors is cited from prior work (deorphanization by the Meyerhof group) and was not remeasured here. This study's own novel finding is receptor-subtype-selective pharmacochaperone activity in HEK293T cells. This is a heterologous expression cell system, and there is no human perceptual data.
This versatility is put to use outside the laboratory as well. A document on the sensory analysis of wine lists a concentration of quinine sulfate as the reference solution for training panelists to detect bitterness.
quinine is used as the sensory reference stimulus for bitternesscontextual
Scope: Part I, Table 1 of the same document. A table of guideline reference-solution concentrations used to train candidate sensory panelists in stimulus detection.
Note: In the alternative ISO 3972 table accompanying the same table, caffeine at 0.195 mg/L (the concentration detected and identified by 50% of novice subjects) is separately listed as the bitterness identification criterion.
Sets quinine sulfate at 6 mg/L as the reference solution for bitterness, and separately lists caffeine at 0.195 mg/L as the identification criterion in the alternative ISO 3972 table.
Limitations: Not a value indicating the bitterness intensity of any particular wine — merely a guideline stimulus concentration for training.
The same compound has also been adopted as a yardstick in the training of alcoholic-beverage tasting panels. In a threshold measurement of brewing-course trainees, sensitivity to quinine sulfate showed large individual variation, and that sensitivity tended to overlap with sensitivity to other tastes as well.
quinine has human taste thresholds of Mean detection threshold 7.2×10⁻⁶M (quinine sulfate, equivalent to 0.0006%)supported
Scope: Measured by Pfaffmann's single-point identification method in 28 trainees (19-40 years old, mean 25.61, including 1 woman) attending the 78th brewing course at the National Tax Agency's Brewing Research Institute. Of the 4 taste substances (glucose, malic acid, salt, quinine sulfate), quinine sulfate showed the largest individual variation, with a coefficient of variation (σ/x̄×100) reaching 136%. Subjects sensitive to quinine sulfate also tended to be sensitive to malic acid and salt.
Note: Oba et al. (1984). Note that this is baseline data for training and standardizing the discrimination ability of an alcoholic-beverage tasting panel (including sake), rather than a measurement of sake itself.
Mean stimulus thresholds for the 4 substances were: glucose 4.69×10⁻²M, malic acid 1.9×10⁻⁴M, salt 1.26×10⁻²M, and quinine sulfate 7.2×10⁻⁶M. There was individual variation in sensitivity to the 4 tastes, and subjects sensitive to quinine sulfate tended to also be sensitive to malic acid and salt.
Limitations: This is a baseline threshold measurement for training an alcoholic-beverage tasting panel, not a sensory evaluation of sake itself.
Even so, the scale of this yardstick itself is not monolithic. Lining up two studies that measured the human threshold for quinine hydrochloride, the relationship in which the detection threshold should be lower than the recognition threshold is reversed, and the reported values differ by an order of magnitude.
quinine has a reported human taste threshold of About 0.011-0.018 mM (recognition threshold, QUEST/qYN, 2019) versus 0.264-0.809 mg/mL ≈ 0.67-2.0 mM (detection threshold, QUEST, 2026) — the detection threshold should be ≤ the recognition threshold, yet the two diverge by roughly 2 orders of magnitude in the higher directioncontested
Scope: Human psychophysical measurement in healthy adults. Both studies presented quinine hydrochloride by spraying it onto the anterior tongue (2019: about 0.2 mL of mist onto the front half; 2026: a spray onto the front 2/3)
Note: The molar conversion (mg/mL → mM, using an anhydrous quinine HCl MW of ≈360.9) is our own derived value. The methods (detection vs. recognition, concentration series, judgment procedure) and panels differ (n=41, mean age 30 vs. n=100, ages 33-57, 86% female). Within Juratli 2026 alone, the value moves by about 3-fold from test 0.809 to retest 0.264 mg/mL. A case in point that no single 「キニーネ閾値」 (in translation: "quinine threshold") exists.
Recognition threshold for quinine hydrochloride (log10 mM): QUEST test -1.737 (SD 1.101), retest -1.889 (SD 0.953). qYN test -1.974 (SD 0.952), retest -1.980 (SD 0.962) — that is, about 0.010-0.018 mM. Stimulus: about 0.2 mL of mist sprayed onto the front half of the tongue. The concentration series ran across 21 log10 steps from 0.077e-3 mM to 3.131 mM.
Limitations: A recognition, not detection, criterion. A young sample with normal BMI. A test-retest SD of about 1 log unit indicates substantial between-person variability.
Contradicts: QUEST spray detection threshold for quinine hydrochloride: test 0.809 (± 0.374) mg/mL, retest 0.264 (± 0.082) mg/mL (the ± as given in the table header; n=79/78), with the solution sprayed onto the front two-thirds of the tongue; the series ran across 18 levels from 0.00015-1.23 mg/mL. Despite using a looser detection criterion, these values are roughly 2 orders of magnitude higher than the 2019 recognition threshold, and test and retest differ by about 3-fold even within the same study.
Limitations: Differs from the 2019 study in concentration series, spray volume and coverage area, and population; an ICC of 0.567 indicates moderate reproducibility; the direction of the discrepancy (detection higher than recognition) is our own comparison, and neither paper discusses it.
Show datacompound-quinine —has_reported_human_taste_threshold_of→ "About 0.011-0.018 mM (recognition threshold, QUEST/qYN, 2019) versus 0.264-0.809 mg/mL ≈ 0.67-2.0 mM (detection threshold, QUEST, 2026) — the detection threshold should be ≤ the recognition threshold, yet the two diverge by roughly 2 orders of magnitude in the higher direction"
Quinine's bitterness moves when combined with other tastes. In human taste tests, relatively high concentrations of sucrose, aspartame, and sodium chloride have been confirmed to weaken perceived bitterness.
quinine — perceived bitterness is suppressed by: Relatively high concentrations of sucrose, aspartame, and sodium chloridesupported
Scope: 0.1 mM quinine hydrochloride, in the human study cited
Note: The concentration required and the matrix are essential to interpretation.
Verbatim quotation from the abstract: An almost 80% inhibition of bitterness (calculated as concentration %) of a 0.1 mM quinine hydrochloride solution required 800 mM of sucrose, 8 mM of aspartame, and 300 mM NaCl. Sucrose, aspartame, and NaCl were all effective, but only at relatively high concentrations, and aspartame was about 100 times more efficient than sucrose on a molar basis. Phosphatidic acid (1.0 w/v%) and tannic acid (0.05 w/v%) reached comparable inhibition (81.7% and 61.0%) at far lower concentrations. In binding experiments, quinine did not bind to NaCl, sucrose, or aspartame, with the unbound fraction for these compounds close to 100%, which the authors attribute to these compounds being hydrophilic.
Limitations: An aqueous-solution test in which a 5 ml sample was held in the mouth for 15 s with a 20 min interval between samples; there is no food matrix. The panel comprised 11 volunteers, a small size for magnitude estimation. Because bitterness was scored on a 5-point scale anchored to quinine standard solutions of 0.01-1.00 mM, the reported percentages are inhibition rates converted to concentration, not a direct drop in scale value.
An independent human study on salt-bitter binary mixtures, using quinine hydrochloride as the bitter stimulus and NaCl, LiCl, KCl, L-arginine:L-aspartic acid, sodium acetate, and sodium gluconate as salts at 0, 0.1, 0.3, and 0.5 M, reports that perceived bitterness was suppressed by salt in most cases, though the degree of suppression varied. For urea, 3 sodium salts and a lithium salt all suppressed bitterness while KCl did not, identifying the active ingredient as the sodium or lithium ion, with an effect independent of perceived saltiness.
Limitations: The abstract does not isolate the magnitude of suppression specific to quinine, and the detailed ion analysis was carried out for urea rather than quinine. Panel size is not given in the abstract. The concentrations here (0.1-0.5 M NaCl) lie in a similarly high range to the 300 mM NaCl of Nakamura 2002, consistent with this claim that suppression requires relatively high concentrations.
Limits: Reports that binary taste-mixture interactions are not a fixed property of human taste but vary with PROP taster status. Using the sucrose/quinine hydrochloride and NaCl/quinine hydrochloride mixtures among 4 pairs, supertasters rated all qualities and overall mixture intensity higher than medium and non-tasters, and in the sweet-bitter mixture, non-tasters did not show the suppression of sweetness intensity at the highest QHCl concentration that was evident in super- and medium tasters.
Limitations: The group difference stated in the abstract concerns the suppression of sweetness by quinine, not the suppression of quinine's bitterness by sucrose or NaCl. The abstract has no explicit statement about group differences in bitterness suppression. This therefore limits the generality of a single suppression value but does not directly contradict it. Group size is not given in the abstract.
This movement is not necessarily one-directional, however. In an experiment within the same framework, adding tannic acid at a low concentration weakened quinine's bitterness, while at a higher concentration a reversal was observed in which the bitterness score instead rose above the control.
quinine can show higher bitterness scores under: Tannic acid suppresses quinine bitterness to about 61% of the control up to 0.05 (w/v)%, but at 0.15 (w/v)% this reverses and the bitterness score exceeds the control (the direction of the effect flips with dose).preliminary
Scope: The specific concentrations used in the cited human study.
Note: This is presented as an example of interaction between descriptors, not as proof that astringency is a form of bitterness.
The relationship is non-monotonic. Raising tannic acid from 0.005 to 0.05 (w/v)% lowered the bitterness score of 0.1 mM quinine to about 61% of the control, but at 0.15 (w/v)% no further inhibition occurred — suppression weakened, and the resulting bitterness score of 1.5 was significantly higher than the control level. The unbound quinine fraction remained at about 72%, and unlike phosphatidic acid, tannic acid does not compete strongly at the receptor site (an adsorption effect of about 27.5% plus masking of the remaining receptor site of nearly 33%, totaling 61.0%), so the authors attribute this reversal not to a change in binding but to the astringency of the high-concentration tannic acid solution itself.
Limitations: The authors themselves state explicitly that the explanation by astringency is unproven, and the astringency intensity data are described as not shown. Because bitterness and astringency were rated on the same bitterness scale, the increase at 0.15 (w/v)% may partly reflect confusion between descriptors rather than a true increase in bitterness. Aqueous solution only; panel of 11.
Show datacompound-quinine —can_show_higher_bitterness_scores_with→ "Tannic acid suppresses quinine bitterness to about 61% of the control up to 0.05 (w/v)%, but at 0.15 (w/v)% this reverses and the bitterness score exceeds the control (the direction of the effect flips with dose)."
Beyond measuring bitterness, there is also an organized picture of the process for hiding it. A review covering oral pharmaceutical dosage forms divides taste-masking approaches into two mechanism classes.
pharmaceutical taste masking is divided into 2 mechanism classes: (1) Interference with taste transmission. Uses flavor chemicals or bitterness inhibitors that compete with the drug in exciting taste receptor cells. (2) Prevention of the release of the unpleasant-tasting drug into the oral cavity. Uses ion-exchange resins, solid dispersions, polymer coatings, prodrugs, microencapsulation, liposomes, nanoemulsions, and cyclodextrin inclusion complexessupported
Scope: Oral pharmaceutical dosage forms. A classification presented in a 2023 systematic review of cyclodextrin taste masking
Note: EMA lists a compatible but differently organized set of measures (choice of excipients including taste maskers, changing particle size, an alternative salt, coating the active substance, coating the dosage form, complexing agents such as cyclodextrins, and reducing free drug in solution). Neither source reports a comparison of effectiveness between the classes.
Context: The guideline lists measures for improving palatability: judicious choice of excipients (including bitterness maskers, sweeteners, and flavors), changing the particle size of the active substance or excipients, choosing an alternative salt of the active substance, coating the active substance, coating the final dosage form, use of complexing agents (for example, cyclodextrins), and, for liquid formulations, reducing the amount of free active substance in solution. It also instructs that alternative approaches to improving taste (coating, complex formation, choice of base, viscosity adjustment) be considered where relevant.
Limitations: A list of options organized by formulation measure rather than by mechanism, with no comparative effectiveness data.
This review divides taste-masking strategies into 2 groups by the mechanism through which taste is transmitted. The first group interferes with the taste-transmission pathway using flavor chemicals and bitterness inhibitors, with the flavoring agent competing with the drug in exciting taste receptor cells. The second group prevents the unpleasant-tasting drug from being released into the oral cavity, using ion-exchange resins, solid dispersions, polymer coatings, prodrugs, microencapsulation, liposomes, and nanoemulsions; cyclodextrin inclusion is one method within this second category.
Limitations: The 2-group classification is the review authors' own framework and is not attributed to a primary source. Because the review's own search terms are centered on cyclodextrins, its listing of non-cyclodextrin methods is background information rather than a systematic survey.
Show dataprocess-pharmaceutical-taste-masking —is_divided_into→ "2 mechanism classes: (1) Interference with taste transmission. Uses flavor chemicals or bitterness inhibitors that compete with the drug in exciting taste receptor cells. (2) Prevention of the release of the unpleasant-tasting drug into the oral cavity. Uses ion-exchange resins, solid dispersions, polymer coatings, prodrugs, microencapsulation, liposomes, nanoemulsions, and cyclodextrin inclusion complexes"
There is also an example showing how this classification plays out in an actual formulation. One report states that applying a process combining cyclodextrin and a sweetener to a pediatric decoction containing Platycodon root changed the evaluation from 「受け入れ難い」 (in translation: "difficult to accept") to 「後に残る苦味のない甘さ」 (in translation: "sweet with no lingering bitterness"). Of the two mechanism classes, this is an example of the class that suppresses the drug's own exposure through inclusion complexation, rather than the class that interferes with taste transmission.
Scope: A water decoction of a pediatric formulation containing Platycodon root
Note: The division of roles: HP-beta-CD suppresses residual bitterness and astringency, while xylitol improves mouthfeel.
Verbatim: "An optimized combination of 6.5% HP-β-CD plus 10% xylitol (w/w relative to PR) successfully transformed PR decoctions from 'difficult to accept' to 'sweet with no lingering bitterness'." This was also corroborated by electronic-tongue DFA.
Limitations: Based on the abstract. Verified in 2 formulations.
Standing In for the Tongue — the Electronic Tongue
Measuring bitterness with the human tongue is a laborious task. Standing in for it is an instrument called the electronic tongue, a chemical-sensor device. Its individual sensors are not dedicated units that respond only to a specific substance; instead, the overlapping signals are put through statistical processing and read back out as a taste evaluation. For a group of drugs that trained volunteers rated against a quinine hydrochloride reference, one report states that a statistical model derived from the electronic tongue's signals reproduced most of the variation in the human scores. Once drugs of differing chemical character are lined up across each other, however, the bitterness ranking given by the electronic tongue and the ranking given by human thresholds stop agreeing. Here again, quinine is placed as the reference connecting the machine's evaluation to the human one.
electronic tongue (taste sensing system) can predict human bitterness ratings of Drugs in solution. The reported agreement is high for chemically similar, charged (ionized) drugs (R2 = 0.910 with the Insent SB2BT0 sensor, R2 = 0.9621 with the ASTREE PLS model, both against 11 trained volunteers who rated 8 H1-receptor antagonists using quinine hydrochloride as the anchor), but ranking agreement breaks down across a chemically heterogeneous set of drugscontested
Scope: Oral drug formulation development. The evidence base reviewed in Pharmaceutics 2024 (55 projects over the past 10 years) and Frontiers in Chemistry 2024
Note: Both the supporting observation and the contradicting observation come from the same 2024 review, which presents both side by side. The reviewers' own summary is that the electronic tongue can succeed as an evaluation of bitterness rather than a prediction of it, but that correlation with human data is still needed even so.
2 independent panels of 11 trained volunteers each rated 8 H1-receptor antagonists against anchor solutions of quinine hydrochloride (0.01, 0.03, 0.1, 0.3, and 1 mM). Multiple regression on the Insent SB2BT0 sensor signal, its CPA value, and adsorption capacity reproduced the human scores at R2 = 0.910, and a PLS model against 2 ASTREE sensors (AB, JE) reproduced them at R2 = 0.9621. Because these drugs share similar physicochemical properties, the review points out that this is an evaluation approach rather than a predictive one.
Limitations: A chemically homogeneous drug set, all cationic. The review itself downgrades this result from prediction to evaluation. The primary study has not been read here.
Contradicts: A 2006 ASTREE study ranked drugs at 10 mM, by PCA Euclidean distance from water, from least to most bitter as: ranitidine HCl > prednisolone Na > quinine HCl ~ phenylthiourea > paracetamol >> sucrose octaacetate > caffeine. Lining up the same substances by previously published human taste thresholds instead gives sucrose octaacetate <= quinine HCl < phenylthiourea <<< caffeine < paracetamol, and the review states that this cannot be compared with the electronic tongue's ranking. The review also notes that ranitidine HCl, ranked most bitter by the electronic tongue, was given only a probability of 0.737 of being bitter by a bitterness-prediction web server, while sucrose octaacetate, a known bitter acetylated sugar, was predicted to be sweet with a probability of 0.752.
Limitations: The review itself states that this comparison is debatable: the electronic-tongue samples at 10 mM are far above human threshold concentrations, and non-ionic drugs (phenylthiourea, paracetamol, caffeine) are ranked alongside ionic drugs, even though the electronic-tongue system detects the latter far better. No human threshold data at all could be found for ranitidine HCl or prednisolone sodium, and these 2 were excluded from the human-side ranking.
Limits: Of 55 e-tongue taste-masking projects published in the preceding 10 years, 26 presented in vivo data (human or rodent) validating the e-tongue results, covering 36 drugs. Correlation between in vivo and e-tongue data worked especially well for ionized drugs, particularly those with properties close to the H1 antihistamines, while difficulties arose for uncharged substances. The conclusion is that the e-tongue is qualified for taste-masking evaluation only for at least some projects and specific drugs, and that correlation with human data continues to be necessary because the biological taste system is too complex to be fully modeled by an artificial sensor.
Limitations: Fewer than half of the projects involved in vivo validation, and the domain of applicability is defined mainly by the studies that chose to validate.
Limits: The review states that a correlation exists between electronic-tongue output and conventional human taste-panel methods, but that it is not always consistent. This is because it depends on the type of electronic tongue, sensor selection, signal processing, data analysis, standardization of the tasting method, and evaluator training, and also because the electronic tongue's perceptual mechanism and sensitivity differ from a human's, so it may not fully capture individual taste perception. This relationship therefore requires calibration and validation specific to the sample and conditions, and cannot be generalized.
Limitations: This is a methodological position statement rather than new data. The primary study cited as grounds for the high correlation (a model for matrine, oxymatrine, and berberine hydrochloride with R2 0.8955-0.99965) has not been read here.
Show dataconcept-electronic-tongue —can_predict_human_bitterness_ratings_of→ "Drugs in solution. The reported agreement is high for chemically similar, charged (ionized) drugs (R2 = 0.910 with the Insent SB2BT0 sensor, R2 = 0.9621 with the ASTREE PLS model, both against 11 trained volunteers who rated 8 H1-receptor antagonists using quinine hydrochloride as the anchor), but ranking agreement breaks down across a chemically heterogeneous set of drugs"
The human threshold for quinine hydrochloride ought to be measured similarly whether by detection or by recognition, yet different sources report values differing by an order of magnitude, and it is not shown which difference in measurement conditions that gap comes from.
The electronic tongue's ability to reproduce human bitterness scores is limited to comparisons among chemically similar, charged drugs. The review itself acknowledges that it cannot be used for ranking across drugs of differing character.
The name denatonium benzoate also comes up alongside quinine as a bitterness reference substance. However, no material found among what was read here describes an actual scene in which this substance is used as a reference, and that gap is left open here.
Frequently asked
How is the bitterness of medicine hidden?
A review covering oral pharmaceutical dosage forms organizes methods for hiding bitterness into two broad groups. One uses flavoring agents or bitterness inhibitors that interrupt the very pathway that carries bitterness. The other — through ion-exchange resins, solid dispersions, polymer coatings, microencapsulation, or inclusion in cyclodextrins, among others — prevents the bitter component itself from coming out into the mouth in the first place. In an example combining cyclodextrin and a sweetener with a pediatric decoction containing Platycodon root, one report states that the evaluation changed from 「受け入れ難い」 (in translation: "difficult to accept") to 「後に残る苦味のない甘さ」 (in translation: "sweet with no lingering bitterness"). No data comparing which method is most effective is found among the material confirmed here.
How is the strength of a medicine's bitterness measured?
In human taste tests, a method has been used in which solutions of quinine hydrochloride are mapped to bitterness levels by concentration, and the bitterness of other drugs is then compared against that yardstick. Solutions of quinine sulfate have also been adopted as the reference solution for bitterness in the training of wine sensory panels and in threshold measurements for alcoholic-beverage tasting panels. More recently, a method has also come into use in which signals are measured with a chemical-sensor device called the electronic tongue, and a statistical model is used to estimate human scores. However, the electronic tongue is reported to agree well only when comparing chemically similar drugs, and the ranking is reported to stop agreeing once drugs of differing character are compared across each other.
Is taste the main reason children are reluctant to take medicine?
In a survey of 153 children aged 3-10, 58.2% of the children who responded said they had experience of refusing to take medicine, and among the children who gave a reason, 84.9% cited taste or flavor. The proportion citing difficulty swallowing or a feeling of the throat catching stayed at only 8.1%. This is, however, self-reported information about past experience, and not a survey that measured whether the medicine was actually kept up. How much weight individual differences in taste reception carry has not yet been established — the authors themselves state that prospective research is needed.