title: Taste masking analysis in pharmaceutical formulation development using an electronic tongue.
abstract: The purpose of this study is to assess the feasibility for taste masking and comparison of taste intensity during formulation development using a multichannel taste sensor system (e-Tongue). Seven taste sensors used in the e-Tongue were cross-selective for five basic tastes while having different sensitivity or responsibility for different tastes. Each of the individual sensors concurrently contributes to the detection of most substances in a complicated sample through the different electronic output. Taste-masking efficiency was evaluated using quinine as a bitter model compound and a sweetener, acesulfame K, as a bitterness inhibitor. In a 0.2 mM quinine solution, the group distance obtained from e-Tongue analysis was reduced with increasing concentration of acesulfame K. This result suggests that the sensors could detect the inhibition of bitterness by a sweetener and could be used for optimization of the sweetener level in a liquid formulation. In addition, the bitterness inhibition of quinine by using other known taste-masking excipients including sodium acetate, NaCl, Prosweet flavor, and Debittering powder or soft drinks could be detected by the e-Tongue. These results further suggest that the e-Tongue should be useful in a taste-masking evaluation study on selecting appropriate taste-masking excipients for a solution formulation or a reconstitution vehicle for a drug-in-bottle formulation. In another study, the intensity of the taste for several drug substances known to be bitter was compared using the e-Tongue. It was found that the group distance was 695 for prednisolone and 686 for quinine, which is much higher than that of caffeine (102). These results indicate that the taste of prednisolone and quinine is stronger or more bitter than that of caffeine as expected. Based on the group distance, the relative intensity of bitterness for these compounds could be ranked in the following order: ranitidine HCl>prednisolone Na>quinine HCl approximately phenylthiourea>paracetamol>>sucrose octaacetate>caffeine. In conclusion, the multichannel taste sensor or e-Tongue may be a useful tool to evaluate taste-masking efficiency for solution formulations and to compare bitterness intensity of formulations and drug substances during pharmaceutical product development.
authors.affiliation: Pharmaceutical Sciences R&D, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46225, USA. zhengjy@lilly.com
authors.forename: Jack Y
authors.initials: JY
authors.lastname: Zheng
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Keeney
mesh_terms: D015374:Biosensing Techniques / Q000295:instrumentation; D002626:Chemistry, Pharmaceutical; D011239:Prednisolone / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D013549:Sweetening Agents / Q000145:classification* / Q000494:pharmacology; D013649:Taste; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D013843:Thiazines / Q000494:pharmacology; D014059:Tongue / Q000187:drug effects; D014173:Transistors, Electronic
chemical_list: D013549:Sweetening Agents; D013843:Thiazines; D011239:Prednisolone; D011803:Quinine; C006362:acetosulfame