Taste Sensing system Application Report No.6
Intelligent Sensor Technology, Inc.

Nov.11.2015

Formulating better tasting pediatric drug is just as important as better adherence. The development of drug that are easily
taken orally is very important especially for pediatric or geriatric patients, as is the efficiency of drug. We would like to introduce
3 cases of drug formulation development work by Japanese pharmaceutical company(originator) for which our taste sensing
system played an active role in taste adjustment between placebo and active drug or finding appropriate bitterness maskingagent for the API.
Case 1:
Taste tuning of Placebo and Active drug for clinical trial at an early phase of development.
Background :Simplified Formulation like solution or suspension is commonly applied forClinical trial rather than producing complex solid dosage form at early phaseof development stage. API’s taste in simplified formulation is directly exposed,
so it is required to formulate the taste of placebo and active drug as similar taste
as possible for a more reliable clinical trial. It is difficult to know the taste of APIat early phase of development due to its safety aspect. This is an exampleof how our customer use the system for this kind of work.

Taste sensing system TS-5000Z

Application :The company developed new API which has Free form and Phosphate form. The taste of Free form is stable at any
concentration although they observe Phosphate form has bitterness and sourness(Fig.1).

Fig.1 Sourness and Bitterness sensor outputs of suspen-

Fig.2 Sourness and Bitterness sensor outputs ofsion of New drugs under Early Phase of Development.

Suspensions of New drugs and Placebo solution

Suspension base(×), Free form drug in low conc(□),

Citric acid solution in low concentration(□),

in moderate conc(△), in high conc(○)

in moderate conc(△), in high conc(○)

Phosphate drug in low concentration(■),

Phospharic drug in low concentration(■),

in moderate conc(▲), in high conc(●)

in moderate conc(▲), in high conc(●)
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From the result of (Fig.1), it is suggested that salt form affects to taste of suspension rather than API’s own taste. (Fig.2) isshowing the bitterness and sourness intensity of various concentrations of citric acid solution and Phospharic drug solution.
They show similar taste tendency that assures the similar taste profile of placebo and active drug.

Case 2 :Taste masking of API in jelly dosage drug
Background :Jelly dosage is sometimes chosen as an effective dosage
form for geriatric or people who has difficulty in swallowing.
In general, taste masking of jelly form is more difficult thansolid dosage form as masking method is limited.
They tried to apply a polysaccharide to reduce bitternessof API.
Application :(Fig.3) is showing bitterness sensor response to0.2% of different polysaccharide added with 0.04% API.
It is suggested that Carrageenan can reduce bitternessof API effectively in order ι,λ and κ type.

Fig.3 Effect of Masking Agents on Donepezil Hydrochloride
solution

They consider interaction between cationic API andanionic polymers leads API’s molecular weight growth,then it reduces chance in bonding to taste bad on human
tongue(lipid membrane in sensor).
(Fig.4) is showing taste stability test of 3, 5 and 10mg
API contained jelly dosage drug. The control and36months stored at 5 degree C are tested .
In addition, 0.01, 0.1 and 1mM API solution are measured
to compare.

Fig.4 Sourness and Bitterness Sensor Outputs of Stability
Sample for 36months of ARICEPT Oral Jelly Formulation
and Donepezil Hydrochloride solution
3mg/5℃(○), 3mg/25℃(●), 5mg/5℃(△),
5mg/25℃(▲), 10mg/5℃(□), 10mg/25℃(■)
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What is Taste sensing system?
Employs the same mechanism as the human tongue to measure initial & aftertaste through artificial lipid membrane sensors
that interpret taste reception of drugs, beverages or foods as numerical data.
What is different between chemical analysis and taste sensing system?
It is not realistic to express taste by chemical analysis. For example, it is said that hundreds of substances are contained incoffee that contribute to its taste. HPLC can give us precise answer in quantitative and qualitative number of them but it isdifficult to convert those data into numerical taste information. For example, even though the amount of caffeine(bitternesslevel) is the unchanged, the bitterness level seems to change after adding in the sugar. The amount of bitterness has notchanged, but the taste can change depending on what is in the mix. This is called taste interaction. Taste sensing system canmeasure taste interaction. That is the reason it is widely applied in pharmaceutical company who requires measurement oftaste suppression or enhancement.
How many sensors are used?
We can measure 5 basic tastes and Astringency. Umami(Savoriness), Bitterness and Astringency can be measured for initialand aftertaste separately. The sensor is the most unique feature in this system. There are 8 sensors available corresponding
to each taste. Each sensor selectively responds to each taste and sensor output is adjusted with human threshold and intensity.
There are 3 different bitterness sensors, one is mainly used for food or drug and two are used for mainly drug.
What kind of drug or food can the system measure?
Any sample can be measured, as long as it is in liquid form. When testing drugs,

Sourness1086
4
20-2-4-6-8-10

Richnessfrom umami

we usually dissolve API or drug in 10mMKCl solvent to give it some conductivity.
When testing foods, we usually use purified water to dissolve or mix with samples

Saltinessto extract the taste. Removal of oil to less than 2% is recommended for optimum
sensor conditions.

Umami

How long does it take for measurement?

Bitterness

Astringent

Bitterness from ion

Aftertaste fromastringency

Aftertaste frombitterness

40 minutes per one sample. 90% of the total time is consumed for sensor
washing and sensor stabilization.
Is there any sample which the system cannot measure?
Neutral substances. The sensor reads electric potential difference sensor andReference electrode. The principal is similar to mechanism of human taste sensory.

References: YAKUGAKU ZASSHI 134(3)325-331(2014)

Disclaimer: This information is for reference only, and is not proof of absolute taste quality of samples, nor guarantee data repeat-ability.

Manufactured byDistributed byIntelligent Sensor Technology, Inc.

Higuchi inc.(Los Angeles office)5-1-1 Onna, Atsugi, Kanagawa, Japan 2430032

2281 W.205th St, Suite A-107, Torrance, CA 90501

taste.sensor@insent.co.jp

morinaga@usa.higuchi-group.com(T)+81-46-296-6609(T)310-212-7234

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