Quantifying the bitter masking effect of drug-cyclodextrin complexation: NMR-ROESY mixing time approach

• Published in: Carbohydrate research 2024-03, Vol.537, p.109067-109067, Article 109067
• Main Authors: Ueda, Tomohiko, Yamaguchi, Mei S., Christian-Tabak, Leela, Takai, Yoshiaki, Tode, Chisato
• Format: Article
• Language: English
• Subjects: beta-Cyclodextrins; bitter masking effect; Cyclodextrin; Cyclodextrins; Humans; Inclusion complex; mixing time; NMR-ROESY; Solubility; Taste
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2024.109067

Taste, especially unpleasant taste, can be key for patient compliance. In the formulation development process, drug-cyclodextrin (CD) inclusion complexes are often used to improve the solubility of a drug and/or mask its bitterness. This study aimed to evaluate the bitter masking effect of CDs on different drugs using NMR-ROESY analysis, human sensory tests, and e-tongue measurements. The strength of inclusion complex formation between drugs and CDs was investigated by NMR-ROSEY, and these results were compared to human sensory test results. In the sensory test, participants identified which drug-CD inclusion complexes were not bitter. NMR-ROSEY results aligned with the sensory tests; short magnetization transfer times corresponded to masked bitterness. The electrical tongue was not able to detect the taste of any of the drug-CD inclusion complexes. Additionally, we used NMR-ROSEY to determine which drug-CD inclusion complex formed in a system with multiple drug substances present. This research offers valuable insights into the bitter masking effect of CDs on different drugs and presents a comprehensive evaluation approach using various methods. This knowledge has significant implications for the pharmaceutical industry, clinical practice, and patient care, contributing to improved patient compliance and satisfaction with bitter medications. The object of this manuscript is to build the easy, rapid and strong, safety and ethical method of evaluating bitter masking effect of CDs which could be applied in all the pharmaceutical phase and field. Taste of the drugs, especially the bitterness can be a great stress to patient whom suffers from the illness. To evaluate the drug bitterness, the human sensory taste tests may provide the TRUE taste result; which has safety and ethical concerns. Electric tongues (e-tongues) serve as an alternative method for evaluating drug bitterness, but they face challenges when analyzing neutral compounds in varying concentrations due to the way e-tongues measure bitterness through the electrochemical cell's cathodic and anodic potentials. To address this issue, we hypothesized that a shorter NMR-ROESY mixing time indicates stronger drug-CD interaction, thus leading to more efficient bitter masking. The Correlation hypothesis of bitterness and proximity between drugs and CD by the NMR-ROESY method Experimental hypothesis figure showing the shorter mixing time reveals efficient bitter masking effect due to detecting the stronger