Chem. Pharm. Bull. 54(3) 310—314 (2006)

instructions in infants and children are unsavory or bitter taste, formulations which are very powdery, and multiple dosings. Powdery medicines in particular often taste unpleasant, even in taste-masked formulations. Recently, a number of jelly products have been developed that aim to improve compliance by aiding swallowing. When the drug is incorporated in the jelly product, swallowing is made easier due to its moderate adhesion and liquidity while drug adsorption by the tongue is prevented, and bitterness perception is thereby decreased. Fukui has reported on the physicochemical characteristics of jellies, such as viscosity, strength, loss of water content, and its effect on swallowing. There are, however, few reports in which jellies have been evaluated from the viewpoint of bitterness suppression. We have already quantitatively evaluated the bitterness of several human pharmaceuticals using the taste sensor. In particular, the relation between the concentration of various pediatric antibiotics and their bitterness intensity has been investigated, as well as the effect of mixing the drugs with various beverages on palatability. The usefulness of the taste sensor in predicting the bitterness of these antibiotic mixtures was confirmed. In the present study, we evaluated bitterness suppression of dry syrups containing the macrolides clarithromycin (CAM) or azithromycin (AZM), both of which are extremely bitter, by the addition of jellies, using gustatory sensation tests and the taste sensor. The concentrations of CAM and AZM in solutions extracted from physical mixtures of dry syrup and jelly were determined by HPLC. Finally, dissolution tests were performed on a mixture of dry syrup and chocolate jelly and on dry syrup alone to confirm the equality of dissolution profile. Experimental Materials Two macrolide dry syrups were used in this study: clarithromycin, CLARITH dry syrup for pediatric use (CAMD), purchased from Taisho Toyama Co., Ltd., Tokyo, Japan, and azithromycin, ZITHROMAC Fine Granules for Pediatric Use (Commercially available from December, 2004) (AZMD) purchased from Pfizer Pharmaceutical Co., Ltd., Tokyo, Japan. The following jellies were used in this study: Okusurinometane ·Chocolate (Chocolate jelly) (Ryukakusan Co., Ltd., Tokyo, Japan), Paste-jouno oblate ·Plane (Paste jelly) (Sanwa kagaku kenkyusho Co., Ltd., Aichi, Japan), Water Jelly·Muscat (Water jelly) (Ohki Co., Ltd., Tokyo, Japan). All other reagents were of special reagent grade. Sample Preparation For human gustatory sensation testing, pH measurement, concentration measurements, and the dissolution test, 10 ml of the jelly (or water as control) was mixed with 0.2 g of CAMD or AZMD uniformly for 30 s with spoon. Two additional mixtures of CAMD and chocolate jelly, containing 0.13 g and 0.4 g of CAMD, were prepared to examine the effect of the ratio of the amount of chocolate jelly to CAMD on bitterness. For the taste sensor samples, 0.1 mmol of KCl was added to improve the sensitivity of the sensor. Gustatory Sensation Tests Gustatory sensation tests were performed using the method of Katsuragi et al. The standard quinine hydrochloride concentrations used were 0.01, 0.03, 0.10, 0.30, and 1.00 mM and the corresponding bitterness scores were defined as 0, 1, 2, 3, and 4, respectively. Before testing, the well-trained healthy adult volunteers (n 5 or 6) were asked to keep the standard samples in their mouths, and told their concentrations and bitterness scores. After tasting 2 ml of a test drug sample, they were asked to give the sample a bitterness score. The significance of the differences between the bitterness scores was analyzed using Mann-Whitney’s U test. Sensor Measurement and Data Analysis The taste sensor system, SA402B of Intelligent Sensor Technology Co., Ltd., Atsugi, Japan, consists of a sensor component, a mechanically controlled robot arm, and a computer for data analysis. The detecting sensor part of the equipment consists of eight electrodes composed of lipid/polymer membranes which transform information about substances producing taste into electrical signals. The difference between the electric potential of the sensor electrode and that of the reference electrode is measured by means of a high-input impedance amplifier connected to a computer. The taste sensor methodology and sensor membrane components used in the present study are essentially the same as those described in a previous paper. Samples (mixtures of 0.8 g of dry syrup and 40 ml of jelly or water) were evaluated in the following manner. The electrode is first dipped into the ref310 Vol. 54, No. 3 Chem. Pharm. Bull. 54(3) 310—314 (2006)