Liu, Jiaqi; (2025) Cucurbit[7]uril as a Potential Taste-Masking Excipient. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Palatability is central to the acceptability of oral paediatric medicines. The cyclodextrin (CD) family is an established class of taste-masking agents. However, CDs are not always effective, as their binding affinities with guest molecules may be insufficient, especially with soluble bitter drugs that continue to pose significant challenges for taste masking. The macrocycle cucurbit[7]uril (CB7) is an emerging candidate as a pharmaceutical excipient; it is similar in size to HP-β-CD (2-Hydroxypropyl-β-Cyclodextrin, a commonly used CD) but features a more rigid hydrophobic cavity that forms stable complexes with various drugs. This project aimed to explore 2 hypotheses: (1) that the stronger binding affinities of drug-CB7 complexes, relative to drug-HP-β-CD complexes, are associated with better taste-masking efficacy, and (2) that increased ratios of CB7 or HP-β- CD in the complex system enhance taste masking. Soluble bitter model drugs— Quinine HCl, Memantine HCl, Ranitidine HCl, and Chlorpheniramine Maleate— were selected for evaluation. Binding constants for these drugs with CB7 and HP- β-CD were measured using UV/Vis titration, revealing that drug-CB7 binding constants were at least 3.2 times higher (up to 425,000) than those for drug-HP- β-CD in water. In vitro electronic-tongue taste assessments supported the hypotheses, indicating CB7’s potential for taste masking. However, in vivo rat brief-access taste aversion model unexpectedly showed that CB7 provided comparable or even lower taste-masking efficacy than HP-β-CD. This might be attributed to weakened drug-CB7 binding in the rat model, as salivary salts and the basic pH of rat saliva (~8.4) likely triggered drug release from CB7 cavities, negating CB7's binding advantages over HP-β-CD. In conclusion, host-guest complexation is a dynamic, changeable binding system; its taste-masking efficacy needs to be assessed under buccal biorelevant conditions to ensure accurate clinical reflection.

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