Zaleplon The Development Of The Sublingual Spray

Zaleplon is a kind of non-benzodiazepine sedative hypnotic drugs. It is used clinically for the treatment of insomnia. It can markedly shorten the time of falling asleep with good curative effect and few side effect. The dosage forms of Zaleplon mainly used on domestic and aboard clinical practice is tablet and capsule. Because of a serious liver first-pass effect, the absolute bioavailability of the oral administration was only 30%. At the same time , oral administration takes on action slowly. In order to provide an alternative administration of Zaleplon for systemic drug delivery to increase its absorption and improve patient compliance, considering the physiochemical properties of Zaleplon and the characteristics of sublingual administration, we planed to study on the sublingual spray of Zaleplon.The optimization of the formulation was the key work in our study. After selection of dosage, solvent, correctant and administration instrument, the formulation of the dosage form was detemined. A series of samples were prepared for quality criterion study, stability study. The result showed that the formulation of the dosage form was reasonable, simple and convenient to prepare, with good reproductivity.In order to control the quality of the preparation, a reliable HPLC method of determination of Zaleplon and its relative substances was established. Under the condition of test, the pharmaceutical aids and the decomposition products could be well separated from Zaleplon. The stability study on Zaleplon sublingual spray indicated that it was stable, nearly without any changes during the stability study. On base of formulation study and stability study, quality criterion studies were put forward. It was proved that the draft of quality criterion for the dosage form could well control the quality of products.The pharmacokinetics and bioavailability study of the sublingual spray of Zaleplon was carried out on 6 Beagle dogs in a randomized crossover manner. The result indicated that the concentration- time curves conformed to 1–compartment model with first-order absorption. The new dosage form took on action faster than oral administration. It was absorbed about 1 times faster than tablet, Tmax was 37.5min and Cmax was 415.5ng/mL, about 1 times higher than tablet. The bioavailability of it was 157.6% and it was bioequivalent to tablet.No report about Zaleplon sublingual spray was found. This study has its innovation and appli- cation value in clinics. The preclinical study of it as 2nd category new drug of China have been finished basically. Patent of it has been applied in process, filed No.was 200710175243.9...