An Electronic Tongue: Evaluation of the Masking Efficacy of Sweetening and/or Flavoring Agents on the Bitter Taste of Epinephrine

Abstract

Abstract. 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. Tastemasking 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.

Citric Acid Suppresses the Bitter Taste of Olopatadine Hydrochloride Orally Disintegrating Tablets

“…Rachid et al showed that citric acid suppressed the bitterness of epinephrine by using the taste evaluation using an e-tongue. 9) Calcium imaging analysis also indicated that citric acid inhibited the response of hTAS2R16, one of the human bitter taste receptors, to salicin. 10) In addition, Lawless et al demonstrated that citric acid suppressed the bitterness of calcium chloride by using human gustatory sensation tests.…”

“…Similarly, citric acid is used in drug formulations such as "gummy" formulations. 8) Some studies, by using an electronic tongue 9) and calcium imaging analysis of human bitter taste receptor hTAS2R, demonstrated that citric acid can suppress the bitterness of drugs. 10) However, these studies were performed using solutions and not ODTs.…”

Sublingual Diffusion of Epinephrine Microcrystals from Rapidly Disintegrating Tablets for the Potential First-Aid Treatment of Anaphylaxis: In Vitro and Ex Vivo Study

“…Previously, we developed Epi RDSTs that retain sufficient hardness to withstand shipping and handling but disintegrate rapidly (≤30 s) to release Epi (12)(13)(14)(15)(16). In a validated rabbit model, we demonstrated that the rate and extent of absorption after administration of an Epi 40 mg RDSTs was similar to the rate and extent of absorption after administration of Epi 0.3 mg intramuscular (IM) through an EpiPen the sublingual mucosa and achieve the required plasma epinephrine levels.…”

Traditional Human Taste Panel and Taste Sensors Methods for Bitter Taste Masking Research on Combined Bitterness Suppressants of Berberine Hydrochloride

“…Recently, research into drug taste masking has been highlighted in the popular press (2)(3)(4)(5) with taste masking using bitterness suppressants (BSs) as an important topic. (6)(7)(8)(9)(10) BSs compensate for the bitter substance by blocking bitter taste receptors, truncating the bitterness signal transmission or by offering an even greater signal to the sweet receptors. BSs have different mechanisms.…”