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.