Preparation and pharmacokinetics of flumazenil sublingual tablet / 药学实践与服务

ABSTRACT

Objective To prepare flumazenil sublingual tablets and study its bioavailability. Methods Flumazenil sublingual tablets were prepared by compressing flumazenil inclusion compound with hydroxypropyl-β-cyclodextrin as the inclusion material. In a double-cycle crossover trial, twelve beagle dogs were randomly divided into two groups, one group receiving flumazenil sublingual tablets and the other receiving flumazenil injections. LC-MS method was developed and validated to determine flumazenil plasma concentration. The pharmacokinetic parameters and bioavailability were calculated using WinNonlin pharmacokinetic software. Results In the pharmacokinetic study, AUClast of flumazenil injection and sublingual tablet was （8.41±2.15） and （8.86±2.83） h·ng·ml−1, respectively; Cmax was （10.96±2.62） and （6.36±2.14） ng/ml, respectively; tmax was （0.18±0.05） and （0.58±0.24） h, respectively. The bioavailability of flumazenil sublingual tablet was 52.68%. Conclusion Clathrates were used to prepare flumazenil sublingual tablets to achieve safe and efficient delivery. LC-MS method was established for the determination of flumazenil plasma concentration, and the advantages were simple, accurate and sensitive.