Cyclodextrins (CD) are widely used bitter taste masking agents, for which the binding equilibrium constant (K) for the drug-CD complex is a conventional parameter for quantitating the taste masking effects. However, some exceptions have been reported to the expected relationship between K and bitterness reduction and the relationship between kinetic parameters of a drug-CD interaction, including association rate constant (K-a) and disassociation rate constant (K-d), and taste masking remains unexplored. In this study, based upon a database of kinetic parameters of drugs-HP-beta-CD generated by Surface Plasmon Resonance Imaging for 485 drugs, the host-guest kinetic interactions between drugs and HP-beta-CD for prediction of taste masking effects have been investigated. The taste masking effects of HP-beta-CD for 13 bitter drugs were quantitatively determined using an electronic gustatory system (alpha-Astree e-Tongue). Statistical software was used to establish a model based on Euclidean distance measurements, K-a and K-d of the bitter drugs/HP-beta-CD-complexes (R-2 = 0.96 and P < 0.05). Optimized parameters, K-a(3), K-d, K-a, k(d) K-d(3), K-a(2) and K-a/K-d with notable influence, were obtained by stepwise regression from 12 parameters derived from K-a, K-d and K (K-a/K-d). 10-fold cross-validation was used to verify the reliability of the model (correlation coefficient of 0.84, P < 0.05). The established model indicated a relationship between K-a, K-d, K and taste masking by HP-beta-CD and was successful in predicting the extent of taste masking by HP-beta-CD of 44 bitter drugs, which was in accordance with the literature reported. In conclusion, the relationship between kinetics of drug-CD interactions and taste masking was established and providing a new strategy for predicting the cyclodextrin mediated bitter taste masking. (C) 2017 Elsevier B.V. All rights reserved.
[1]Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, 501 Haike Rd, Shanghai 201203, Peoples R China.
[2]Univ Bradford, Sch Med Sci, Bradford BD7 1DP, W Yorkshire, England.
[3]Shanghai Univ Tradit Chinese Med, Engn Res Ctr Modern Preparat Technol Tradit Chine, Minist Educ, Shanghai 201203, Peoples R China.
(8.0+极速模式)