Guo Zhen, Wu Fei, Singh Vikramjeet, Guo Tao, Ren Xiaohong, Yin Xianzhen, Shao Qun, York Peter, Patterson Laurence H, Zhang Jiwen
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.
Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
J Pharm Biomed Anal. 2017 Jun 5;140:232-238. doi: 10.1016/j.jpba.2017.03.042. Epub 2017 Mar 20.
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) and disassociation rate constant (K), 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, K and K of the bitter drugs/HP-β-CD-complexes (R=0.96 and P<0.05). Optimized parameters, K, K, KK, K, K and K/K with notable influence, were obtained by stepwise regression from 12 parameters derived from K, K and K (K/K). 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, K, 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.
环糊精(CD)是广泛使用的苦味掩蔽剂,药物 - CD复合物的结合平衡常数(K)是定量掩味效果的常规参数。然而,K与苦味降低之间的预期关系以及药物 - CD相互作用的动力学参数(包括缔合速率常数(K)和解离速率常数(K))之间的关系存在一些例外情况,而掩味关系仍未得到探索。在本研究中,基于表面等离子体共振成像产生的485种药物与HP-β-CD的动力学参数数据库,研究了药物与HP-β-CD之间的主客体动力学相互作用以预测掩味效果。使用电子味觉系统(α-Astree电子舌)定量测定了HP-β-CD对13种苦味药物的掩味效果。使用统计软件基于苦味药物/ HP-β-CD复合物的欧几里得距离测量值、K和K建立模型(R = 0.96,P <0.05)。通过从K、K和K(K / K)导出的12个参数进行逐步回归,获得了具有显著影响的优化参数K、K、KK、K、K和K / K。使用10倍交叉验证来验证模型的可靠性(相关系数为0.84,P <0.05)。所建立的模型表明了K、K、K与HP-β-CD掩味之间的关系,并成功预测了44种苦味药物的HP-β-CD掩味程度,这与文献报道一致。总之,建立了药物 - CD相互作用动力学与掩味之间 的关系,并为预测环糊精介导的苦味掩蔽提供了新策略。