cyclodextrins

Cyclodextrins are oligosaccharides with glucose units arranged in a ring; they have the property of forming a 「ホスト-ゲスト複合体」 (in translation: "host-guest complex") by taking up other molecules in the cavity formed inside. Typically, there are α-, β-, and γ-cyclodextrins composed of 6, 7, or 8 glucose units, as well as substituted derivatives such as hydroxypropyl-β-cyclodextrin. In pharmaceuticals, they are used as solubilizers, stabilizers, and also as additives (excipients) to mitigate bitterness. The mechanism is that by taking up bitter molecules into this cavity and encapsulating them, the concentration of free drug or active components reaching the taste buds is lowered, weakening the perceived bitterness.

In a study adding β-cyclodextrin at 0.25-2% to bitter melon (goya) juice, the 1.5%-supplemented juice showed the highest sensory acceptability score (7.7 +/- 0.3) compared to the control (3.8 +/- 0.7); analysis by NMR and FTIR showed that β-cyclodextrin takes up momordicosides, a bitter component, as an inclusion complex. Another research group had a trained panel rate the bitterness intensity itself of bitter melon extract and reports that adding only 0.25% β-cyclodextrin reduced bitterness by approximately 33%, and adding 0.75% or 1% reduced it by over 90%. This was a larger effect than the 19% reduction with 0.6% carboxymethylcellulose, which was used as a comparison.

In pharmaceutical bitterness masking, it has been reported that the type of cyclodextrin and the molar ratio produce large differences in effect. When fluoxetine was complexed with β-cyclodextrin, volunteers rated non-complexed fluoxetine as bitter or very bitter, whereas the complexed drug was described as tasteless; captopril was complexed with β-cyclodextrin at a 1:2 molar ratio in an orally disintegrating tablet and was rated more favorably than the non-complexed tablet, which had a metallic, burning flavor. Conversely, it has been reported that even when spironolactone was complexed with hydroxypropyl-β-cyclodextrin, taste was not improved. With cetirizine, a 1:5 solution with β-cyclodextrin led most raters to answer no bitterness or mild bitterness, whereas a solution at the same ratio of γ-cyclodextrin was rated as extremely bitter by most, demonstrating that which cyclodextrin is selected affects the outcome, even for the same drug.

In a study using propranolol, on a taste sensor (electronic tongue) scale where hydroxypropyl-β-cyclodextrin alone was 0 and propranolol alone was 10, the bitterness score of a formulation complexed at a 1:1 molar ratio was reported as 8.5 (15% reduction), and at 1:2 as 7.3 (approximately 30% reduction). However, this measurement was instrumental only, without a human sensory panel; in a report cited by another review from a regulatory authority, electronic tongue measurement of the same propranolol in a marketed pediatric formulation (prepared by a method different from cyclodextrin) showed approximately 80% masking effect, and simple numerical comparison is not possible. Bitterness masking by cyclodextrin requires individual verification for each compound and for each type of cyclodextrin.