title: Host-guest kinetic interactions between HP-β-cyclodextrin and drugs for prediction of bitter taste masking.
abstract: 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 (Ka) and disassociation rate constant (Kd), and taste masking remains unexplored. In this study, based upon a database of kinetic parameters of drugs-HP-β-CD generated by Surface Plasmon Resonance Imaging for 485 drugs, the host-guest kinetic interactions between drugs and HP-β-CD for prediction of taste masking effects have been investigated. The taste masking effects of HP-β-CD for 13 bitter drugs were quantitatively determined using an electronic gustatory system (α-Astree e-Tongue). Statistical software was used to establish a model based on Euclidean distance measurements, Kaand Kdof the bitter drugs/HP-β-CD-complexes (R2=0.96 and P<0.05). Optimized parameters, Ka3, Kd, KaKd, Kd3, Ka2and Ka/Kdwith notable influence, were obtained by stepwise regression from 12 parameters derived from Ka, Kdand K (Ka/Kd). 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 Ka, Kd, K and taste masking by HP-β-CD and was successful in predicting the extent of taste masking by HP-β-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.
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Medical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Vikramjeet
authors.initials: V
authors.lastname: Singh
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Ren
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Medical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Yin
authors.affiliation: School of Medical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
authors.forename: Qun
authors.initials: Q
authors.lastname: Shao
authors.affiliation: School of Medical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: York
authors.affiliation: School of Medical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom. Electronic address: l.h.patterson@bradford.ac.uk.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Patterson
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jwzhanggroup@163.com.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D007700:Kinetics; D015203:Reproducibility of Results; D013649:Taste
chemical_list: D000073738:2-Hydroxypropyl-beta-cyclodextrin
keywords: Cyclodextrin; Kinetic parameters; Modeling; Prediction; Surface plasmon resonance imaging; Taste masking