Netsu Sokutei, 39 (W39), p. 6, (2012)


Inhibitory Effect of Cyclodextrin on Complexation of Risperidone with Tea Catechin

Risperidone (RISP) is an antipsychotic agent indicated for the acute and maintenance treatment of schizophrenia. Taking an oral solution containing RISP with the green tea, the efficacy was surely decreased by forming the complexes between RISP and the tea catechin. In this study, the inhibitory effect of cyclodextrin (CD) on complexation of RISP with (-)-epigallocatechin gallate (EGCg) in the solution was clarified by isothermal titration microcalorimetry (ITC). Both solutions of RISP (2.4 mM) and EGCg (2.4 mM) at pH 3.5 were mixed, then RISP in filtrate was reduced to 64%. In the mixed solution adding β-CD, however, RISP in filtrate was recovered to 100% approximately. According to the measurement at pH 3.5 and 298K by ITC, EGCg formed the insoluble complex with RISP at associate constant (K) of 8.45 x 102 M-1 exothermically, ΔH = -14.8 kJ·mol-1, and formed the complex with β-CD (K = 2.10 x 104 M-1, ΔH = -29.6 kJ·mol-1). While, little heat of reaction between RISP and β-CD was observed and the calorimetric titration curve for the mixed solutions of RISP and EGCg with β-CD was almost same as that for EGCg-β-CD system. From the results, it was indicated that the complexation between RISP and EGCg in oral solution could be inhibited by adding β-CD to include EGCg into the β-CD cavity.