Abstract

Technologies for quantifying bitterness are essential for classifying medicines. As previously reported, taste sensors with lipid polymer membranes can respond to bitter hydrochloride substances in pharmaceuticals. However, the acid hydrolysis reaction between the lipid phosphoric acid di-n-decyl ester (PADE) and the plasticizer tributyl o-acetylcitrate (TDAB) led to a deterioration in sensor responses during storage. Given the cost of transportation and preservation for commercialization, membrane components that maintain physical and chemical stability during long-term storage are needed. Here we present a membrane electrode based on hydrophobic tetrakis [3,5-bis (trifluoromethyl) phenyl] borate (TFPB) and a plasticizer 2-nitrophenyl octyl ether (NPOE) for the quantification of pharmaceutical bitterness; they maintain a stable response before and after accelerated deterioration, as well as high selectivity and sensitivity. It is a first attempt to use a completely dissociative substance to replace non-completely dissociative lipids. Our work offsets the long-term stability issue of a bitterness sensor with a negatively charged hydrophobic membrane. Meanwhile, we provide the opportunity to select surface charge modifiers for a membrane surface using ester plasticizers containing oppositely charged impurities.

Highlights

  • Taste plays a vital role in the acceptance of a pharmaceutical formulation

  • We revealed that the reason behind the deterioration is that the phospholipid phosphoric acid di-n-decyl ester (PADE) creates hydrogen ions, which promote tributyl o-acetylcitrate (TBAC) hydrolysis [17]

  • The purpose of this paper is to develop a bitterness sensor for quantifying pharmaceutical bitterness with high stability in long-term storage

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Summary

Introduction

Many active pharmaceutical ingredients (APIs) have a bitter taste, and are aversive for children, and for many adults [1]. To deal with this problem, the evaluation of bitterness has become an important step during the process of pharmaceutical development [2]. In the past few decades, several studies on electronic tongues have been drawing intense research interest because of their potential application in taste assessment [3,4,5,6,7,8,9]. The use of an electronic tongue, called a “taste sensor,” provides an objective solution for taste evaluation. The taste sensor is an analytical sensor array system with different artificial lipid polymer membranes

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