Novel mixed hydrotropic solubilization of Zaleplon: Formulation of oral tablets and in-vivo neuropharmacological characterization by monitoring plasma GABA level

作者：Abdelbary Ghada A; Amin Maha M^*; Abdelmoteleb Mostafa

来源：JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 2016, 33: 98-113.

DOI：10.1016/j.jddst.2016.03.014

• Zaleplon
• Hydrotropic solubilization
• Mixed hydrotropy
• Insomnia
• Plasma GABA level

Zaleplon (ZP) is a poorly water-soluble non-benzodiazepine hypnotic drug indicated for the short-term treatment of insomnia having a bioavailability of about 30%. The aim of the present study is to enhance the solubility and consequently the bioavailability of ZP using hydrotropic agents (HA). The solubility of ZP increased about 350- and 2000-fold, respectively, when 1 M of sodium benzoate and resorcinol were used as hydrotropic agents. The optimized mixed hydrotropic tablet formula (F5) composed of Resorcinol:Sodium benzoate microparticles prepared by solvent evaporation technique in a ratio of 4:1 wow exhibits a significantly higher (p < 0.05) in-vitro dissolution (Q5 min) of 31.7 +/- 0.11% after five minutes (Q(5min)) compared to 10.0 +/- 0.10% for Sleep aid (5 mg) respectively. The optimized formula (F5) showed significantly higher (p < 0.05) GABA concentration of 122.5 +/- 5.5 mg/mL in plasma compared to 118 +/- 1.00 and 27.8 +/- 1.5 mg/mL for Sleep aid (5 mg) and control taking only saline respectively suggesting a higher neuropharmacological effect of ZP following hydrotropic solubilization.

• 出版日期2016-6