LAUSR

Abstract The current work presents a new approach for nanosizing zaleplon (ZPN) powder aiming for enhancing its dissolution, bioavailability and hypnotic efficacy. Particles are adsorbed onto nanocarriers thereby acquiring their respective nanosizes. Nanoscale zaleplon was prepared by adsorption onto hydroxyapatite (ZHP) or halloysite (ZHA), respectively. Rotary evaporation enabled arrangement of particles onto outer surfaces of nanocarriers, with 100% loading capacity. Dissolution completed within 30 min, with a half-life of 7 min. The particle size was 645 nm for ZHP and 391 nm for ZHA. Drug particles were present at outer surfaces of nanocarriers as deduced from the DSC, XRDP, nitrogen sorption-desorption and as observed in transmission electron microscope (TEM) images. ZHP showed enhanced penetration through cattle nasal mucosa. Permeability coefficient rose from 0.085 cm/h for the untreated ZPN to 0.2 cm/h for the optimized powder with no alteration in the configuration of epithelial tissues. Significant impairment of locomotor activity accompanied by muscle relaxation and decreased coordination was noticed upon intranasal instillation of ZHP to rats. The relative bioavailability of intranasal ZPN in rabbits increased 2.4 times compared to oral Sleep aid® tablets. Therefore, the new adsorption technique enabled the successful preparation of nanoscale powder of zaleplon with enhanced dissolution and bioavailability.