Non-human tools for the evaluation of bitter taste in the design and development of medicines: a systematic review

Abstract

Taste evaluation is a crucial factor for determining acceptance of medicines by patients. The human taste panel test is the main method used to establish the overall palatability and acceptability of a drug product to a patient towards the end of development. Non-human in vitro and in vivo taste-evaluation tools are very useful for pre-formulation, quality control and screening of formulations. These non-human taste assessment tools can be used to evaluate all aspects of taste quality. The focus of this review is bitterness because it is a key aspect of taste in association with the development of medicines. In this review, recent in vitro (analytical) and in vivo (non-human) tools are described for the assessment of the bitter taste of medicines. Their correlations with human taste data are critically discussed. The potential for their use in early screening of the taste of active pharmaceutical ingredients (APIs) to expedite paediatric formulation development is also considered.

Taste evaluation of a novel midazolam tablet for pediatric patients: In vitro drug dissolution, in vivo animal taste aversion and clinical taste perception profiles

“…Electronic taste evaluation may be a better alternative (11) as it can profile the taste characteristic of the drug molecule via an array of sensors (12). Compared to in vivo models, electronic sensors also provide a more objective and consistent taste evaluation without incurring the ethical and safety concerns associated with using animal and human participants.…”

Comparative in vitro and in vivo taste assessment of liquid praziquantel formulations

“…Furthermore, in vitro methods were developed despite drug release studies which are mostly based on determined taste thresholds in humans. Such in vitro methods involve electronic taste-sensing systems (electronic tongues) or cell based systems using calcium imaging (Mohamed-Ahmed et al, 2016;Slack et al, 2010). The most useful non-human taste assessment tools are the electronic tongue and the BATA model (Mohamed-Ahmed et al, 2016).…”

“…They can provide an early screening of new drugs of unknown toxicity and the relative optimization of preclinical formulations (Mohamed-Ahmed et al, 2016). As a prerequisite for the assessment of multicomponent solutions, a calibration for the pure compounds needs to be performed proving a concentration dependent signal.…”

“…Besides the electronic tongue and in terms of readiness, the rodent brief-access taste aversion (BATA) model is the most useful non-human taste assessment tool. Indeed various parameters (necessary time for data collection, ability to screen pure drugs and formulations, correlation to human in vivo data, validation potential and costs) were graded higher comparatively to other tools by Mohamed-Ahmed et al (Mohamed-Ahmed et al, 2016). Several studies showed the great potential of rat models designed for the measurement of the palatability of different compounds (Bhat et al, 2005) and the correlation to human taste panels (Clapham et al, 2012;Devantier et al, 2008;Noorjahan et al, 2014;Rudnitskaya et al, 2013;Soto et al, 2016).…”

“…Due to the short period of time of exposure to samples, the intake of each compound is limited, to avoid toxic side effects. New chemical entities with unknown toxicity and well-known pharmaceutical compounds can be screened in early development as pure drugs or in preclinical or clinical formulations (Mohamed-Ahmed et al, 2016).…”