The Relationship between Bitter Taste Sensor Response and Physicochemical Properties of 47 Pediatric Medicines and Their Biopharmaceutics Classification

Abstract

The purpose of this study was to investigate the relationship between response to the bitterness taste sensor and physicochemical parameters of 47 pediatric medicines and to classify these medicines according to the biopharmaceutics classification system (BCS). Forty-seven bitter compounds, most of which were on the WHO model list of essential medicines for children (March 2017), were used in the study. Solutions (0.1 mM) were evaluated by an artificial taste sensor using membranes sensitive to bitterness. On the basis of principal component analysis of taste sensor measurements, chlorpromazine, haloperidol, propranolol, amitriptyline, diphenhydramine were predicted to express the strongest levels of basic bitterness, surpassing that of quinine. Correlation tests between bitter taste sensor outputs and physicochemical properties were then carried out and the compounds classified in terms of their biopharmaceutical properties. High log P values (≥2.82), physiological charge (≥1), low log S values (< 3) and small polar surface area (PSA; <45.59 Å 2 ) were found to correlate significantly with the responses of bitter taste sensors. Forty-one of the 47 compounds could be placed into one of four groups in the BCS, on the basis of dose number (D 0 ), an indicator of solubility which takes into account clinical dosage, and fractional absorption (Fa). For medicines classified in group 4, the factors D 0 > 1 and Fa < 0.85 significantly correlated with the responses of the taste sensor for basic bitterness. It was concluded that lipophilicity, physiological charge, solubility, PSA and D 0 are the main factors affecting the bitterness of pediatric medicines.

Combining Powder Formulations of Drugs with Food and Beverages to Improve Palatability

“…In a previous study, Uchida et al reported that acidic beverages should be avoided when taking powder formulations of macrolide antibiotics because the acidic beverage was found to produce a strongly bitter taste, as stated in the information sheet for Clarith ® dry syrup. 22,23) Because azithromycin also belongs to the macrolide antibiotic class of medicines, orange juice might increase the bitterness of azithromycin with the same mechanism. In our study, the sport drink (pH 3.5) and orange juice (pH 3.6) were mild acidic solutions, the other drinks were in a neutral range (pH = 6.0-7.5).…”

“…Previously, some studies were reported to evaluate the bitterness of some medicines quantitatively using a taste sensor. [21][22][23][24][25] The research of taste sensors has made a breakthrough by achieving high selectivity for each taste, especially bitterness. For example, Tanigake et al evaluated the bitterness intensity of clarithromycin with some beverages by a taste sensor.…”

Multi-Methodological Quantitative Taste Assessment of Anti-Tuberculosis Drugs to Support the Development of Palatable Paediatric Dosage Forms

“…The field of in vitro taste assessment is continually evolving. For the Insent etongue, a new taste sensor BT0 has been introduced but was not available at the time of our study; it was designed to be more useful for evaluating the bitterness of hydrochloride salt compounds [34]. Moreover, in recent years, bioelectronic tongues (BioETs), integrating biological materials and various types of transducers, have been proposed to bridge this gap between chemical sensors and biological taste [42].…”

“…In exploring the relationship between the physicochemical properties of paediatric drugs of various Biopharmaceutical Classification System (BCS) class drugs and their bitter baste sensor response, the dose number (D0) was used by Haraguchi et al [34]. This took not only the solubility of the drug but also the highest dose taken with a 250 mL glass of water in account.…”

Evaluation of the Palatability of Dry Syrups and the Bitterness Intensities of Dry Syrups Mixed with Various Beverages

“…Taste sensor SA402B (Intelligent Sensor Technology Inc., Atsugi, Japan) was used to measure the electric potential of the sample solutions (at the same con-centrations as those used in human gustatory sensation testing) in order to predict their taste. Sensor AC0, developed specifically to detect the bitterness of basic substances [14] [15] [16], was used in these experiments. The taste sensor measurements were performed to evaluate bitterness intensity for amlodipine besilate [6], solifenacin succinate [7], H 1 -receptor antagonists [9] and topiramate [17] as described in previous articles.…”