Early pediatric formulation development with new chemical entities: Opportunities of e-tongue besides human taste assessment

Abstract

The palatability of a pediatric drug formulation is one of the key prerequisites for therapeutic success. Liquid formulations are often chosen for pediatric drug products, and they require special attention regarding their taste, as they have direct contact to the taste buds and a relatively long residence time in the oral cavity. For ethical reasons, the role of electronic tongues in the development of oral drug formulations with new chemical entities (NCEs) for pediatric use is growing, however, little is known about the strategies how this instrumental taste assessment can be performed. The present study illustrates two possibilities to combine in-vitro and in-vivo data for the characterization of the palatability of the new drug candidates CSE3104 and CSE3165. As a first step, the implementation and suitability of electronic tongue measurements has been demonstrated by comparison of in-vivo and in-vitro data. In alignment with the taste assessment results during a single-center, double-blinded, randomized, placebo-controlled, single ascending dose (SAD) study in healthy subjects, the bitter taste perception of CSE3104 was assessed with e-tongue measurements. Moreover, the sensor response pattern showed comparable results of the e-tongue measurements to the human taste study of CSE3165: With increasing concentration, the bitterness values were increased. In addition, the human taste pattern showed increasing values for sourness due to higher volumes of the citric acid buffer. Results of the hedonic descriptor "unpleasant" within the human taste assessments could be related to bitterness in the instrumental taste assessment. For the second step in electronic tongue guided formulation development two possibilities are depicted in the article focusing on the effect of different excipients on the formulation on the one hand and on the assessment and comparison of two drug formulations on the other hand. Based on these results, the low number of healthy volunteers for the taste assessment in a Phase 1 study led to a meaningful interpretation, by applying in addition the electronic tongue. Using this instrumental approach led to reproducible data versus the human taste assessment, without ethical concerns, and with a reduction in time and costs.

Keywords: Human taste assessment; Market formulation; NCE; Phase I dose escalation study.