Study On A Sublingual Tablet Of G-0268

Sleeping is a main subject of human health. Because of the intension of modern living style, many people have sleeping problems. Insomnia influences their life quality negatively. Because of the complexities of the insomnia mechanism, pharmaceutical scientists have mainly focused on the development of novel drugs for a long time. However there is no significant progress on the drug discovery till now. The routes used to administrate this kind of drugs are oral, intravenous and intramuscular.G-0268 is a benzodiazepine drug developed by Japan in 1960s. It was introduced into the world market. G-0268 is primarily for the cure of insomnia. Its administration routes are oral, intravenous and intramuscular. The clinical pharmacokinetics study of human being showed that after the administration by the oral route, the Tmax is 2h. The aim of this paper is to develop a sublingual tablet for the insomnia curing which can take effect quickly.Firstly, solubilization using pH combined with cosolvents and complexant HP-β-CD are investigated for G-0268. The intrinsic solubility of the drug is about 89μg. mL-1. And the drug has an ionizable group with an approximately basic pKa of 3.0. Samples buffered at pH1.0,pH2.0,pH7.0 with various concentrations of the solubilizing agents were used to study the solubilization of G-0268. The solubilization of G-0268 was found much more effective when the drug was presented primarily in ionized form.Secondly, we formulated the G-0268 sublingual tablet. Using dissolution test in vitro, the volumes of the disintegrator and anacid, which incorporated the tablet, were optimized in this section. Then we repeated the preparation to confirm the technique.Thirdly, the stability of G-0268 sublingual tablet was investigated. The HPLC method of stability study was developed. The stability study indicated that the sublingual tablet is stable, nearly without any changes during the stability study.Finally, the pharmacokinetic data and bioavailability was studied on Beagle dogs in vivo. The results indicated that the sublingual tablet was bioequivalent to oral tablet and took effect faster than oral tablet. The Tmax and the MRT of the two preparations have significant difference. The T1/2 have no distinct difference.