Zaleplon Dispersible Tablets And Oral Soluble Tablets And Pharmacokinetic Study

Zaleplon is an excitomotor of ω₁ receptor of Benzodiazepine which was widely used for the treatment of insomnia in clinic. Although zaleplon is well absorbed, its absolute bioavailability is approximately 30% because it undergoes a significant first pass effect. There have several kinds of dosage forms marketed such as tablet and capsule.Basic physical and chemical properties and the stability of zaleplon were investigated. Zaleplon was hardly soluble in water, and the solubility became higher with the increase of achohol in the solvent, and it was insensitive to oxygen, light and moisture. No significant difference in absorption rage among each segment of the intestine in rats by the method of everted gut sac.The formulation of the zaleplon dispersible tablets contained three different disintegrators. The disintegration time of two tablets should less than 3min, the size of all the granules which ere collspsed should less than 710μm. An ultraviolet spectrophotometry was set up to determine the content and the accumulated realease of zaleplon. The optional formulation was obtained through a single-factor examination.The relative bioavailability and pharmacokinetics studies of zaleplon were performed in six healthy dogs, using capsules as the reference. The method of HPLC was established to determine the content of zaleplon in dog plasma. T_max of zaleplon in self-made tablets and reference capsules were 1.750±0.418 h and 1.583±0.204 h respectively, C _max were 1.007±0.072 μg/mL and 1.011±0.222 μg/ml, AUC _0-t were 7.274±0.557 μg·h /ml and 8.291±1.377 μg·h /ml, the relative bioavailability of zaleplon dispersible tablets was 126.7%.The results showed that the improvement of zaleplon's bioavailability wasn't obviously due to a first pass effect of zaleplon. In order to improve the bioavailability, considering to make zaleplon into fast dissolving tablets. The time of the tablets dissolved in 2ml water was used as a criteria and an ultraviolet spectrophotometry was developed to determine the content and the accumulated release of zaleplon. The optional formulation of fast dissolving tablets was obtained by the orthogonal experiment.Using the same method above, the study of pharmacokinetics of the zaleplon fast dissolving tablets in dogs was carried on. The dispersible tablets were used as the reference , T_max of zaleplon in self-made tablets and the reference capsules were 0.917±0.0.204 h and 1.583±0.204 h respectively, C_maxwere 2.003±0.439 μg/mL and 1.011±0.222 μg/mL, AUC _0-t werel2.055±1.283 μg·h /mL and 8.291±1.377 μg·h /mL, the relative bioavailability of zaleplon dispersible tablets was 145.4%.The result showed that the fast dissolving tablets could increase the C_max, shorten the T_max and...