A novel approach to assess and improve palatability of an inhaled asset using the Rat Brief Access Taste Aversion Assay and an <i>In Silico m</i>odel of salivary flow
Creators: name: Andrews, Danielle
name: Ives, Robert
name: Wassell, Emma
name: Fairman, David
Publisher: name: F1000 Research Limited
Year: 2017

description: Patient compliance can be heavily impacted by the palatability of a medicine. This is especially relevant to the paediatric population. When aversive taste is noted in clinic, the need to reformulate can lead to significant delays in getting potentially life changing medicine to the patient. The typical liquid nebulizer deposits 30% to 40% of drug product in to the mouth, where it can interact with Tas2 receptors and potentially cause a taste response.<br> <br>Rats have similar subsets of Tas2 receptors to humans and the brief access taste aversion (BATA) assay can be used to predict aversive taste (Clapham <i>et al</i>, 2012)  before a potential medicine reaches clinic. Activation of TRPM8 receptors (also known as ‘cold receptors’) might reduce perception of bitter taste (Bharate <i>et al</i>, 2012). Both rats and humans possess TRPM8 receptors and use of a suitable agonist, such as menthol could prove advantageous when attempting to mitigate bitter taste of inhaled medicine.<br> <br>Calculating the maximum oral concentration of a drug product administered over time is complicated. Whilst drug product is entering the mouth and increasing oral concentration, saliva is being produced and reducing oral concentration. When the salivary volume exceeds a certain level, a ‘swallow response’ is initiated. By applying certain assumptions regarding salivary flow (Dawes, 2008), differential equations can be used to predict the oral concentration of a drug product at any given time during administration.<br> <br>The presented work uses the BATA assay to investigate whether the rat model can predict the palatability of an inhaled asset at its intended clinical dose. An attempt is then made to activate TRPM8 receptors and observe whether taste perception of the inhaled asset is altered. Data collected using the rat is then translated to human and a mathematical model of salivary flow applied to predict peak oral concentration and longevity of aftertaste.<br> <br>All animal studies were ethically reviewed and carried out in accordance with the Animals (Scientific Procedures) Act 1986 and GSK Policy on the Care, Welfare and Treatment of Animals.<br> <br>REFERENCES:<br>1 - Bachmanov. A., Beauchamp. G. (2009). Taste Receptor Genes. <i>Annu Rev Nutr.</i> 2007: 27. p. 389-414.<br>2 - Bharate, SS., Bharate, SB. (2012). Modulation of thermoreceptor TRPM8 by cooling compounds. <i>ACS Chem Neurosci</i>. 3 (4). p. 248-267.<br>3 - Clapham, D., Kirsanov, D., Legin, A., Rudnitskaya, A., Saunders, K. (2012) Assessing taste without using humans : rat brief access aversion model and electronic tongue. <i>Int J Pharm</i>. 435 (2). p. 137-9.<br>4 - Dawes, C. (2008). Salivary flow patterns and the health of hard and soft oral tissues. <i>JADA</i>. 139 (suppl 2). p. 18S-24S.<br>5 - Lawless. HT., Heymann. H. (2010). Sensory evaluation of food: principles and practices, 2<sup>nd</sup> Edition. <i>Springer</i>. p. 42-50.