Improved Durability and Sensitivity of Bitterness-Sensing Membrane for Medicines

This paper reports the improvement of a bitterness sensor based on a lipid polymer membrane consisting of phosphoric acid di-n-decyl ester (PADE) as a lipid and bis(1-butylpentyl) adipate (BBPA) and tributyl o-acetylcitrate (TBAC) as plasticizers. Although the commercialized bitterness sensor (BT0) has high sensitivity and selectivity to the bitterness of medicines, the sensor response gradually decreases to almost zero after two years at room temperature and humidity in a laboratory. To reveal the reason for the deterioration of the response, we investigated sensor membranes by measuring the membrane potential, contact angle, and adsorption amount, as well as by performing gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found that the change in the surface charge density caused by the hydrolysis of TBAC led to the deterioration of the response. The acidic environment generated by PADE promoted TBAC hydrolysis. Finally, we succeeded in fabricating a new membrane for sensing the bitterness of medicines with higher durability and sensitivity by adjusting the proportions of the lipid and plasticizers.

[1]  Kiyoshi Toko,et al.  Development of sweetness sensor with selectivity to negatively charged high-potency sweeteners , 2014 .

[2]  Kiyoshi Toko,et al.  Quantitative prediction of bitterness masking effect of high-potency sweeteners using taste sensor , 2016 .

[3]  Maria H. O. Piazzetta,et al.  Microfluidic electronic tongue , 2015 .

[4]  Kiyoshi Toko,et al.  Study of the Relationship between Taste Sensor Response and the Amount of Epigallocatechin Gallate Adsorbed Onto a Lipid-Polymer Membrane , 2015, Sensors.

[5]  Gui Xinjing,et al.  Traditional Human Taste Panel and Taste Sensors Methods for Bitter Taste Masking Research on Combined Bitterness Suppressants of Berberine Hydrochloride , 2017 .

[6]  Bipan Tudu,et al.  A review on combined odor and taste sensor systems , 2016 .

[7]  W. G. S.,et al.  Sense of Taste , 1888, Nature.

[8]  Kiyoshi Toko,et al.  Examination of Amount of Astringent Substances Adsorbed Onto Lipid/Polymer Membrane Used in Taste Sensor , 2014 .

[9]  D. Correa,et al.  Detection of trace levels of organophosphate pesticides using an electronic tongue based on graphene hybrid nanocomposites. , 2017, Talanta.

[10]  Xavier Cetó,et al.  Development and application of an electronic tongue for detection and monitoring of nitrate, nitrite and ammonium levels in waters , 2013 .

[11]  Fredrik Winquist,et al.  Voltammetric electronic tongues – basic principles and applications , 2008 .

[12]  Patrycja Ciosek,et al.  Sensor arrays for liquid sensing--electronic tongue systems. , 2007, The Analyst.

[13]  G. Beauchamp,et al.  Taste receptor genes. , 2007, Annual review of nutrition.

[14]  Kiyoshi Toko,et al.  Development of a Sweetness Sensor for Aspartame, a Positively Charged High-Potency Sweetener , 2014, Sensors.

[15]  Kiyoshi Toko,et al.  Relationship between Taste Sensor Response and Amount of Quinine Adsorbed on Lipid/Polymer Membrane , 2012 .

[16]  Shobha Ghosh,et al.  The mammalian amiloride‐insensitive non‐specific salt taste receptor is a vanilloid receptor‐1 variant , 2004, The Journal of physiology.

[17]  K. Hayashi,et al.  Multichannel taste sensor using lipid membranes , 1990 .

[18]  K. Toko,et al.  Quantification of suppression of bitterness using an electronic tongue. , 2001, Journal of pharmaceutical sciences.

[19]  Daniel Citterio,et al.  Smart taste sensors. , 2008, Analytical chemistry.

[20]  Kiyoshi Toko,et al.  Electronic Tongues–A Review , 2013, IEEE Sensors Journal.

[21]  Kaiqi Su,et al.  Recent achievements in electronic tongue and bioelectronic tongue as taste sensors , 2015 .

[22]  Kiyoshi Toko,et al.  Relationship between the Amount of Bitter Substances Adsorbed onto Lipid/Polymer Membrane and the Electric Response of Taste Sensors , 2014, Sensors.

[23]  Kiyoshi Toko,et al.  Selectivity control in a sweetness sensor using lipid/polymer membranes , 2005 .

[24]  Kiyoshi Toko,et al.  Quantification of tastes of amino acids using taste sensors , 2013 .

[25]  Tai Hyun Park,et al.  Human taste receptor-functionalized field effect transistor as a human-like nanobioelectronic tongue. , 2013, Nano letters.

[26]  Kiyoshi Toko,et al.  Advanced Taste Sensors Based on Artificial Lipids with Global Selectivity to Basic Taste Qualities and High Correlation to Sensory Scores , 2010, Sensors.

[27]  Ítala M. G. Marx,et al.  Sensory classification of table olives using an electronic tongue: Analysis of aqueous pastes and brines. , 2017, Talanta.

[28]  V. Anand,et al.  The latest trends in the taste assessment of pharmaceuticals. , 2007, Drug discovery today.

[29]  Kiyoshi Toko,et al.  Development of an Artificial Lipid-Based Membrane Sensor with High Selectivity and Sensitivity to the Bitterness of Drugs and with High Correlation with Sensory Score , 2009 .

[30]  Kiyoshi Toko,et al.  Research on the Changes to the Lipid/Polymer Membrane Used in the Acidic Bitterness Sensor Caused by Preconditioning , 2016, Sensors.

[31]  M. Valle.  Electronic Tongues Employing Electrochemical Sensors , 2010 .

[32]  Yayoi Kawano,et al.  Preparation of orally disintegrating tablets with taste-masking function: masking effect in granules prepared with correctives using the dry granulation method and evaluation of tablets prepared using the taste-masked granules. , 2010, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.