Kojima Honami, Haraguchi Tamami, Ikegami Saeri, Nishikawa Haruka, Yoshida Miyako, Ozeki Minoru, Kawasaki Ikuo, Uchida Takahiro
Faculty of Pharmaceutical Sciences, Mukogawa Women's University.
Chem Pharm Bull (Tokyo). 2019;67(12):1284-1292. doi: 10.1248/cpb.c19-00548.
The purpose of the study was to prepare a poly-γ-glutamic acid hydrogel (PGA gel), to evaluate physicochemical properties, its ease of swallowing using texture profile analysis (TPA) and its taste-masking effects on amlodipine besylate (AML) using the artificial taste sensor and human gustatory sensation testing. Using TPA, 0.5 and 1.0% (w/v) PGA gels in the absence of drug were within the range of acceptability for use in people with difficulty swallowing according to permission criteria published by the Japanese Consumers Affairs Agency. The elution of AML from prepared PGA gels was complete within an hour and the gel did not appear to influence the bioavailability of AML. The sensor output of the basic bitterness sensor AN0 in response to AML mixed with 0.5 and 1.0% PGA gels was suppressed to a significantly greater degree than AML mixed with 0.5 and 1.0% agar. In human gustatory sensation testing, 0.5 and 1.0% PGA gels containing AML showed a potent bitterness-suppressing effect. Finally, H-NMR spectroscopic analysis was carried out to examine the mechanism of bitterness suppression when AML was mixed with PGA gel. The signals of the proton nearest to the nitrogen atom of AML shifted clearly upfield, suggesting an interaction between the amino group of AML and the carboxyl group of PGA gel. In conclusion, PGA gel is expected to be a useful excipient in formulations of AML, not only increasing ease of swallowing but also masking the bitterness of the basic drug.
本研究的目的是制备聚γ-谷氨酸水凝胶（PGA凝胶），评估其理化性质，使用质地剖面分析（TPA）评估其吞咽难易程度，并使用人工味觉传感器和人体味觉测试评估其对苯磺酸氨氯地平（AML）的掩味效果。根据日本消费者事务局公布的许可标准，使用TPA测定，不含药物的0.5%和1.0%（w/v）PGA凝胶在吞咽困难人群的可接受范围内。制备的PGA凝胶中AML在1小时内完全溶出，且该凝胶似乎不影响AML的生物利用度。碱性苦味传感器AN0对与0.5%和1.0%PGA凝胶混合的AML的传感器输出抑制程度明显大于与0.5%和1.0%琼脂混合的AML。在人体味觉测试中，含AML的0.5%和1.0%PGA凝胶显示出强效的苦味抑制作用。最后，进行了H-NMR光谱分析，以研究AML与PGA凝胶混合时苦味抑制的机制。AML中最靠近氮原子的质子信号明显向高场移动，表明AML的氨基与PGA凝胶的羧基之间存在相互作用。总之，PGA凝胶有望成为AML制剂中一种有用的辅料，不仅能提高吞咽的 ease of，还能掩盖碱性药物的苦味。
