ABSTRACT
This chapter reviews the evaluation system to quantify the bitterness of several medicines and its suppression using the taste sensor, in order to realize the theoretical design of taste-masking formulations. The sensor responses obtained by some sensors allowed not only the quantitative evaluation of the bitterness of the substance but also interpretation of the perception mechanism and characteristics of bitter substance by using a principal component analysis. Single or multi-regression analysis using the selected factors as explanatory variables allowed us to perform the quantitative evaluation of bitterness for basic drugs, antibiotics, Chinese medicines, nutrients, amino acids, and orally disintegrating tablets. The effects of a
bitterness-receptor antagonist, lipoprotein (BMI-40), could be evaluated using bitter-sensitive sensor, whereas the sweet-sensitive sensor was useful for the prediction of suppressed bitterness by sweeteners. It is hoped that these studies will serve as a step that the taste sensor will be actively used for efficient and effective designing of bitterness making formulation. 10.1 General IntroductionTaste has an important role in the development of oral pharma-ceuticals, with respect to patient acceptability and compliance, and is one of the prime factors determining the market penetration and commercial success of oral formulations, especially in pediatric medicine. Hence, pharmaceutical industries invest time, money and resources into developing palatable and pleasant-tasting products and industries adopt various taste-masking techniques to develop an appropriate formulation. Taste assessment is one important quality-control parameter for evaluating taste-masked formulations. Any new molecular entity, drug, or formulation can be assessed using in vitro or in vivo methods for taste. In vivo approaches include human taste panel studies, electrophysiological methods, and animal preference studies. Several innovative in vitro drug release studies utilizing taste sensors, specially designed apparatus and drug release by modified pharmacopoeial methods have been reported in the literature for assessing the taste of drugs or drug products. The multichannel taste sensor, also known as the taste sensor or electronic tongue, is claimed to determine taste in a similar manner to biological taste perception in humans. Furthermore, such taste sensors have a global selectivity that has the potential to classify an enormous range of chemicals into several groups on the basis of properties such as taste intensities and qualities.The idea to use taste sensor for pharmaceutical purposes is rather new, but not surprising, as taste plays an important role in the development of a pharmaceutical formulation. Especially in children, taste of a medication is important with respect to adherence and compliance. As a lot of active pharmaceutical ingredients exhibit an unpleasant taste, taste masking has therefore become increasingly important. Researchers focusing on pediatric drug development have early considered the use of taste sensor
but they also claimed for more reliable data in order to use the taste-sensing systems as adequate tools in taste assessment.1 In order to put the application of taste sensor for pharmaceutical applications in the right context and to understand the motivations of using these systems in this particular area, a short introduction about taste sensation, taste assessment, and masking of unpleasant taste in medicinal products shall be given here.Basically, taste is transmitted by the interaction of dissolved molecules with different targets located in taste buds on the tongue. The mechanisms of signal transduction after binding of the tasting substance can be different depending on the taste quality. Thus, sour and salty tastes are transmitted via ion channels, whereas bitterness and umami are transmitted via G-protein coupled receptors. Sweet taste can be transmitted by both, ion channels, and G-protein coupled receptors. In addition, interactions of different tastes can occur in the subsequent neural network.2 Further, human taste perception in general does not only happen on the tongue as there are other important factors as for example olfactory perception as well as limbic influences.3A major group of taste-masking strategies focuses on the inhibition of the substance receptor interaction, like for example coating of solid dosage forms or complexation of the drug substance by solid or soluble complexing agents. In addition, research focuses on the development of specific blockade of the taste receptor. Other techniques try to cover the taste by misleading the sensory system as for example by using sweeteners. Established taste-masking technologies for pharmaceutical dosage forms were extensively described by Sohi et al. (2004), Ayenew et al. (2009), and Wagh and Ghadlinge (2009).4-6The assessment of successful taste masking can come along with challenges depending on the particular method, as for example analytical techniques, animal studies or human taste panels.7 In general, human sense of taste can be subject to physiological properties and individual preference. Especially for the pediatric population, a general approach applicable for the specific characteristics of children at different development stages is not available yet8 coming along with additional ethical concerns. The toxicity of new chemical entities plays a major role in early preclinical development and leads to limitations with respect to
taste assessment. Therefore, taste sensor may offer an objective and safe method for comparing different formulations with respect to their taste masking. Depending on the dosage form and based on the taste-masking technology, taste assessment by a taste sensor has to be carried out according to specific measurement setups. The mechanisms of detection by the sensors are different as well.
