Abstract
Taste is crucial for patient acceptability and compliance with prescribed medicines, in particular with pediatric patients. Evaluating the taste of new active pharmaceutical ingredients (APIs) is therefore essential to put in place adequate taste-masking techniques, if needed, which will lead to acceptable palatable formulations. Thus, there is an urgent need to develop and optimize taste assessment methods that could be used at different stages of the drug development process. The aim of this study was to investigate the suitability of the rat brief-access taste aversion (BATA) model as a screening tool for assessment of APIs aversiveness that could predict human taste responses. Presently, the taste intensity of nine marketed APIs known to have different levels of bitter intensity (quinine hydrochloride dihydrate, 6-n-propylthiouracil, sildenafil citrate, diclofenac sodium, ranitidine hydrochloride, caffeine citrate, isoniazid, telbivudine and paracetamol) was investigated at different overlapping concentrations with two in vivo taste assessment methods: the rat BATA model and human taste panels with the intention of determining the drugs’ concentrations to produce half of the maximal rating. Overall there was a strong correlation (R2 = 0.896) between rats IC50 and humans EC50 values. This correlation verifies the BATA model as a rapid and reliable tool for quantitative assessment of API aversiveness. A comparable ranking order was obtained mainly for high and medium aversive compounds, whereas it was less aligned for weakly aversive compounds. It was nonetheless possible to propose a classification of poor taste intensity determined in rats that would predict human taste tolerability.
Highlights
Taste assessment studies have indirectly become essential during pharmaceutical development of pediatric medicines due to pediatric regulations in the United States and European Union [1].Evaluating the taste of different derivatives of new chemical entities (NCE) such as salts and isomers during the early stages of the drug development process is of utmost importance to identify taste aversive compounds at screening stages of pharmaceutical development and optimize taste-masking strategies to improve patient adherence and acceptance
The proposed classification made to predict human taste response based on rat brief-access taste aversion (BATA) data is shown on Table 3
The potencies (EC50s) determined in humans were essentially the same as those determined in rats suggesting that the rat BATA model is predictive of human taste assessment for these categories of compounds
Summary
Taste assessment studies have indirectly become essential during pharmaceutical development of pediatric medicines due to pediatric regulations in the United States and European Union [1].Evaluating the taste of different derivatives of new chemical entities (NCE) such as salts and isomers during the early stages of the drug development process is of utmost importance to identify taste aversive compounds at screening stages of pharmaceutical development and optimize taste-masking strategies to improve patient adherence and acceptance. The most widely used and gold standard method to evaluate the taste is by a human taste panel This method presents many challenges since the taste assessment of NCEs can only be performed if sufficient toxicological data are available in humans. Human taste data would not usually be available at the time of writing the Pediatric Investigation Plan (PIP) and the final pediatric dose(s) may not be defined until later in the development program [2]. This will result in very limited information about pediatric dosage forms in the PIP whose selection is often influenced by taste-masking opportunities and palatability. Ethical and/or safety approval can limit human taste
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