Faculty of Pharmacy, University of Manitoba, Apotex Centre, 750 McDermot Avenue, Winnipeg, Manitoba, R3E 0T5, Canada.
AAPS PharmSciTech. 2010 Jun;11(2):550-7. doi: 10.1208/s12249-010-9402-3. Epub 2010 Mar 30.
An epinephrine (E) tablet is under development for sublingual (SL) administration for the first-aid treatment of anaphylaxis; however, the inherent bitterness of E may hinder acceptability by patients, especially children. To assess the degree of E bitterness and to predict the masking effects of sweetening and/or flavoring non-medicinal ingredients (NMIs), the potential usefulness of an electronic tongue (e-Tongue) was evaluated. The e-Tongue sensors were conditioned, calibrated, and tested for taste discrimination. Six standard active pharmaceutical ingredients were used to build and validate a bitterness model which was then used to assess E bitartrate (EB) solutions from 0.3-9 mM. Taste-masking efficiency of aspartame (ASP), acesulfame potassium (ASK), and citric acid (CA) each at 0.5 mM was evaluated. Using EB 9 mM, the bitterness score was 20 on a scale of 20 (unacceptable) down to 1 (not detected). When NMIs 0.5 mM were added, neither ASK (17.2, unacceptable) nor was ASP (14.0, limit acceptable) effective in masking the bitter taste. When the combination of ASK and ASP was used, the bitterness score was reduced to 9.2 (acceptable). However, the addition of CA alone resulted in the best reduction of the bitterness score to 3.3 (not detected). Using the e-Tongue, the incorporation of a variety of sweetening and/or flavoring NMIs into a SL tablet of E could be shown to mask its bitter taste by up to 80%. These results should be confirmed by in vivo studies.
一种肾上腺素(E)片剂正在开发舌下(SL)给药,用于过敏反应的急救治疗;然而,E 的固有苦味可能会阻碍患者,尤其是儿童的接受度。为了评估 E 的苦味程度,并预测甜味剂和/或调味非药用成分(NMIs)的掩蔽效果,评估了电子舌(e-Tongue)的潜在用途。对 e-Tongue 传感器进行了条件处理、校准和味觉区分测试。使用六种标准活性药物成分构建和验证了苦味模型,然后用于评估 0.3-9 mM 的 E 酒石酸盐(EB)溶液。评估了阿斯巴甜(ASP)、乙酰磺胺酸钾(ASK)和柠檬酸(CA)每种 0.5 mM 的矫味效率。使用 EB 9 mM,苦味评分为 20(不可接受)至 1(未检测到)的 20 级。当添加 0.5 mM 的 NMIs 时,ASK(17.2,不可接受)或 ASP(14.0,可接受极限)都不能有效掩盖苦味。当组合使用 ASK 和 ASP 时,苦味评分降低至 9.2(可接受)。然而,单独添加 CA 可将苦味评分降低至最佳的 3.3(未检测到)。使用电子舌,可以证明将各种甜味剂和/或调味 NMIs 掺入 E 的 SL 片剂中,可将其苦味掩蔽高达 80%。这些结果应通过体内研究加以证实。