Hashimoto Yoshimi, Matsunaga Chiharu, Tokuyama Emi, Tsuji Eriko, Uchida Takahiro, Okada Hiroaki
Astellas Pharma Inc., Information System Management Department, 3-17-1 Hasune, Tokyo 174-8612, Japan.
Chem Pharm Bull (Tokyo). 2007 May;55(5):739-46. doi: 10.1248/cpb.55.739.
The purpose of the present study was the quantitative prediction of the bitterness-suppressing effect of sweeteners (sucrose or sugar alcohols) on the bitterness of famotidine (or quinine sulfate as control) solutions using an artificial taste sensor. Firstly, we examined the response characteristics of the sensor response to sweetness. The sensor membrane is charged negatively in the presence of sweeteners, which tend to receive protons from one of the components of the sensor membrane. The magnitude of the sensor response was shown to increase in direct proportion to the concentration of the sweetener. Secondly, we used direct or indirect methods to evaluate and predict the bitterness-suppressing effect of sweeteners on 1 mg/ml famotidine and 81.4 microM quinine sulfate solutions. In direct method, a regression between the sensor output of the sweetness-responsive sensor and the bitterness intensity obtained in human gustatory tests of famotidine solutions containing sweeteners at various concentrations, was performed. As a result, we were able to predict directly the bitterness intensity of the mixed solution. Finally, we also evaluated the bitterness intensity of the dissolution media of commercially available, orally disintegrating tablets containing famotidine by the combined usage of bitterness- and sweetness-responsive sensor. We found that the sugar alcohols in the tablet seem to be effective in the bitterness-suppression of famotidine from these tablets, especially in the initial phase (within 30 s) of the disintegration process.
本研究的目的是使用人工味觉传感器对甜味剂(蔗糖或糖醇)对法莫替丁(或作为对照的硫酸奎宁)溶液苦味的苦味抑制效果进行定量预测。首先,我们研究了传感器对甜味响应的特性。在甜味剂存在的情况下,传感器膜带负电荷,甜味剂倾向于从传感器膜的一种成分中接收质子。传感器响应的幅度显示与甜味剂的浓度成正比增加。其次,我们使用直接或间接方法评估和预测甜味剂对1mg/ml法莫替丁和81.4μM硫酸奎宁溶液的苦味抑制效果。在直接方法中,对甜味响应传感器的传感器输出与在含有不同浓度甜味剂的法莫替丁溶液的人体味觉测试中获得的苦味强度之间进行回归分析。结果,我们能够直接预测混合溶液的苦味强度。最后,我们还通过结合使用苦味和甜味响应传感器评估了含有法莫替丁的市售口腔崩解片溶出介质的苦味强度。我们发现片剂中的糖醇似乎对这些片剂中法莫替丁的苦味抑制有效,尤其是在崩解过程的初始阶段(30秒内)。