A new strategy for taste masking on bitter drug by other combined drug in fixed-dose combination: bitterness of Amlodipine besylate could be masked efficiently by Valsartan
A new strategy for taste masking on bitter drug by other combined drug in fixed-dose combination: bitterness of Amlodipine besylate could be masked efficiently by Valsartan
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DOI：
10.1111/jphp.13134
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发表时间：
2019-07-05
影响因子：
3.3
通讯作者：
Uchida, Takahiro
中科院分区：
文献类型：
--
作者：
Kojima, Honami;Nakamura, Saki;Uchida, Takahiro
目的评价阿苯磺酸钠（AML）与其他5种可能作为固定剂量复方制剂（FDC）使用的抗高血压药物阿拉司琼、贝那普利、氢氯噻嗪、替米沙坦（TEL）和缬沙坦（瓦尔）联合使用时的苦味。方法采用SA 402 B味觉传感器（Intelligent Sensor Technology Inc.）对6种药物单独及与5种药物联合的AML进行苦味评价。AML联合TEL或瓦尔通过味觉传感器和人类味觉测试进行评价。用1H-1-NMR研究AML与TEL或瓦尔的相互作用。在味觉传感器和人味觉测试中，加入瓦尔显著降低了AML的苦味，而加入TEL则保持不变。在AML与瓦尔的H-1-NMR谱中，观察到AML中质子的信号位移与单独AML中的质子的信号位移相比。另一方面，在具有TEL的AML的H-1-NMR谱中，未观察到AML中质子的信号位移。结论瓦尔与AML混合后，AML的正电荷氨基与瓦尔的负电荷四唑基团之间产生静电相互作用，从而抑制了AML的苦味。
Objectives The aim of this study was to evaluate the bitterness of amlodipine besylate (AML) combined with other five antihypertensive drugs: alacepril, benazepril, hydrochlorothiazide, telmisartan (TEL) and valsartan (VAL), which have possibility of usage as a fixed-dose combination (FDC) drugs. Methods The bitterness of individual six drugs and AML combined with each of the five drugs was evaluated using taste sensor SA402B (Intelligent Sensor Technology Inc.). AML combined with TEL or VAL was evaluated by taste sensor and human gustatory sensation tests. The interaction between AML with TEL or VAL was evaluated by H-1-NMR. Key findings The bitterness of AML was significantly decreased by addition of VAL, whereas it remained unchanged by the addition of TEL in taste sensor and human gustatory sensation test. In the H-1-NMR spectrum of AML with VAL, signal shifts of protons in AML were observed compared to that in AML alone. On the other hand, in the H-1-NMR spectrum of AML with TEL, signal shifts of protons in AML were not observed. Conclusions It was suggested that when VAL was mixed with AML, the electrostatic interactions between positive charged amino group of AML and negative charged tetrazole group of VAL were caused, and thereby led the suppression the bitterness of AML.