Improved Durability and Sensitivity of Bitterness-Sensing Membrane for Medicines

Abstract

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.

Taste Sensor: Electronic Tongue with Lipid Membranes

“…On the other hand, the amount of quinine hydrochloride adsorbed to the sensor membrane was the same both before and after the deterioration. 96 The reason for the decrease in CPA value is the same as we reported in a previous study, 97 the CPA value is affected by two factors-the surface charge density and the amount of adsorbed iso-α-acids. The decrease in the CPA value despite the constant amount of adsorbed iso-α-acids is caused by the decrease in the sensitivity of the membrane as the surface charge density increases.…”

“…The results are expressed as the mean ± SD (n = 4). 96 7.3 μg/cm 2 and approximately 5, 15, 43, 70, and 95 mV, respectively. When 0.7% BMI-40 was mixed with a 0.3 mM quinine solution, the amount of quinine adsorbed onto the membrane was reduced by 63%, which indicates that the lipid membrane can be applied to performance evaluations of bitterness-masking substances.…”

“…The deterioration process simulates the deterioration of one year in one month by increasing the ambient temperature and humidity. Figure 12 shows the sensor responses with the contents of lipid PADE before and after the deterioration process; 96 100% PADE means the amount of PADE in the conventional BT0 sensor.…”

“…As a result, only the amount of TBAC was significantly reduced after the deterioration of response, whereas the amounts of PADE and BBAC did not change. 96 Moreover, butyl citrate as the acidic hydrolysis product of TBAC, clearly increased after the deterioration of response, as determined from the result of gas chromatography-mass spectrometry (GC-MS). 96 These results suggest that the phosphoric acid PADE provides protons in the membrane environment and promotes the hydrolysis of TBAC.…”

“…96 Moreover, butyl citrate as the acidic hydrolysis product of TBAC, clearly increased after the deterioration of response, as determined from the result of gas chromatography-mass spectrometry (GC-MS). 96 These results suggest that the phosphoric acid PADE provides protons in the membrane environment and promotes the hydrolysis of TBAC. During long-term storage, the hydrolysate of TBAC produced butyl citrate after deterioration of the response, as explained below.…”