Chitosan and cyclodextrin in intranasal microemulsion for improved brain buspirone hydrochloride pharmacokinetics in rats

The aim of this study was to develop buspirone hydrochloride microemulsion formulations for intranasal administration to improve the drug bioavailability and provide high drug brain levels. For the purpose, chitosan aspartate, and hydroxypropyl-beta-cyclodextrin were incorporated in the microemulsions. The prepared formulations were characterized. Biological investigations including pharmacokinetic studies, brain drug targeting efficiency determinations and histopathological examinations were performed on rats. The results showed that safe and stable mucoadhesive microemulsion suitable for nasal administration were successfully prepared. Ex vivo drug permeation revealed high drug permeation from microemulsions. Absolute bioavailability after intranasal administration of buspirone mucoadhesive microemulsion increased significantly and plasma concentration peaked at 15 min. The AUC(0-360(brain)) was 3 times that obtained after intravenous administration. A high brain targeting efficiency (86.6%) and a direct nose to brain transport (88%) confirmed the direct nose to brain transport of buspirone following nasal administration of the microemulsions. (C) 2013 Elsevier Ltd. All rights reserved.