Brain targeting studies on buspirone hydrochloride after intranasal administration of mucoadhesive formulation in rats

OBJECTIVES: The purpose of this study was to find out whether nasal application of buspirone could increase its bioavailability and directly transport the drug from nose to brain. METHODS: A nasal formulation (Bus-chitosan) was prepared by dissolving 15.5 mg buspirone hydrochloride, 1% w/v chitosan hydrochloride and 5% w/v hydroxypropyl beta-cyclodextrin (HP-beta-CD) in 5 ml of 0.5% sodium chloride solution. The formulation was nasally administered to rats and the plasma and brain concentration compared with that for buspirone hydrochloride solution after intravenous and intranasal (Bus-plain) administration. The brain drug uptake was also confirmed by gamma scintigraphic study. KEY FINDINGS: The nasal Bus-chitosan formulation improved the absolute bioavailability to 61% and the plasma concentration peaked at 30 min whereas the peak for nasal Bus-plain formulation was 60 min. The AUC0-480 in brain after nasal administration of Bus-chitosan formulation was 2.5 times that obtained by intravenous administration (711+/-252 ng/g vs 282+/-110 ng/g); this was also considerably higher than that obtained with the intranasal Bus-plain formulation (354+/-80 ng/g). The high percentage of direct drug transport to the brain (75.77%) and high drug targeting index (>1) confirmed the direct nose to brain transport of buspirone following nasal administration of Bus-chitosan formulation. CONCLUSIONS: These results conclusively demonstrate increased access of buspirone to the blood and brain from intranasal solution formulated with chitosan and HP-beta-CD.