IMPROVEMENT OF THE BIOAVAILABILITY OF BUSPIRONE HCL USING INTRANASAL DELIVERY SYSTEMS

Hamza Bshara

doi:10.21608/ajps.2012.7154

Abstract

The purpose of the present study was to improve the bioavailability of buspirone hydrochloride using oil-in-water microemulsion, which was suggested to be suitable for intranasal delivery. Different pseudo-ternary phase diagrams were constructed to determine the microemulsion existing zone. The optimized microemulsion system was chosen. Different formulations were thus prepared and they were subsequently characterized for their polarized light microscopy, % transmittance, droplet size, and pH. An optimal microemulsion formulation consisting of 5% isopropyl myristate, 50% water, and 45% (w/w) surfactant/cosurfactant [Tween 80 30%, propylene glycol 15 % at 2: 1 weight ratio] was transparent with % transmittance 99.52 ± 0.43%, mean globule size 35.1 ± 0.5nm, and pH 6.4 ± 0.03, was thus selected for preparation of buspirone microemulsion formulation. Drug release was carried out using modified Franz diffusion cell. Various pharmacokinetic parameters including Cmax, tmax and AUC0-t were determined using Wister albino rats as the animal model. The absolute bioavailability (0–6 h) was 15.85% compared to the intravenous administration in rats, whereas the oral bioavailability of buspirone hydrochloride was 4%. The results confirmed that the suggested intranasal buspirone microemulsion formulations improved to a much promising extent its bioavailability.

Highlights

In recent years, the nasal route has received great attention because of the large surface area of the nasal mucosa and the relatively high blood flow, thereby achieving a rapid absorption and avoiding the hepatic first-pass elimination (Lin et al, 2007).Carrier systems play an important role in the drug delivery to the target site because a dosage form with poor drug delivery can make a useful drug worthless
The present study aims was to improve Buspirone HCl (BH) bioavailability using ME that may help maximize the therapeutic index of the drug, reduce its side effects, its dose and its frequency of dosing that may result in a cost-effectiveness treatment intervention (Zhang et al, 2004)
In order to find appropriate oils which can be used for the ME, the solubility of BH was measured in various oils

Summary

Introduction

The nasal route has received great attention because of the large surface area of the nasal mucosa and the relatively high blood flow, thereby achieving a rapid absorption and avoiding the hepatic first-pass elimination (Lin et al, 2007).Carrier systems play an important role in the drug delivery to the target site because a dosage form with poor drug delivery can make a useful drug worthless. Microemulsions (MEs) offer an interesting and potentially powerful carrier system for drug delivery because of their high solubilization capacity, transparency, thermodynamic stability, ease of preparation, in addition to the high diffusion and absorption rates (Jadhav et al, 2006; Yin et al, 2009). Buspirone HCl (BH), the psychotropic drug with selective anxiolytic properties, belongs chemically to the class of azaspirodecanediones which are not chemically or pharmacologically related to benzodiazepines. It seems to be a promising candidate for the intranasal delivery owing to its extensive first-pass metabolism resulting in the poor oral bioavailability of the pure drug (~ 4%), in addition to a short half-life and the poor lower gastrointestinal tract absorption values (Galichet, 2004). The present study aims was to improve BH bioavailability using ME that may help maximize the therapeutic index of the drug, reduce its side effects, its dose and its frequency of dosing that may result in a cost-effectiveness treatment intervention (Zhang et al, 2004)

Objectives

Methods

Results