D-optimal Design for Preparation and Optimization of Fast Dissolving Bosentan Nanosuspension.

Elham Ghasemian,Alireza Vatanara,Parisa Motaghian

doi:10.15171/apb.2016.029

Elham Ghasemian, Alireza Vatanara + Show 1 more

Open Access

https://doi.org/10.15171/apb.2016.029

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Abstract

Bosentan is a drug currently taken orally for the treatment of pulmonary arterial hypertension. However, the water solubility of bosentan is very low, resulting in low bioavailability. The aim of this study was preparation and optimization of bosentan nanosuspension to improve solubility and dissolution rate. The different formulations designed by Design Expert® software. Nanosuspensions were prepared using precipitation method and the effects of stabilizer type and content and drug content on the particle size, polydispersity (PDI) and yield of nanosuspensions were investigated. Particle size, PDI and yield of the optimal nanosuspension formulation were 200.9 nm, 0.24 and 99.6%, respectively. Scanning electron microscopy (SEM) results showed spherical morphology for bosentan nanoparticles. Thermal analysis indicated that there was a partial crystalline structure and change in the pholymorphism of bosentan in the nanoparticles. In addition, reduction of particle size, significantly increased in vitro dissolution rate of the drug. Optimization by design expert software was shown to be a successful method for optimization and prediction of responses by less than 10% error and formulation with 15.8 mg span 85 as an internal stabilizer and 45 mg drug content were introduced as the optimum formulation. The solubility of bosentan in the optimal formulation was 6.9 times higher than coarse bosentan and could be suggested as promising drug delivery systems for improving the dissolution rate and possibly the pharmacokinetic of bosentan.

Highlights

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease that usually characterized by remodeling of the pulmonary vasculature.[1]
Preliminary study on nanosuspension formulation Bosentan nanosuspensions were prepared by the antisolvent precipitation method in the presence of different types of surfactants in aqueous phase
By increasing the drug content in formulation that HPβCD was as an external stabilizer, the size of particles increased

Summary

Introduction

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease that usually characterized by remodeling of the pulmonary vasculature.[1] The progressive vasculopathy increases the pulmonary arterial pressure and pulmonary vascular resistance, eventually culminating in limited patients exercise capacity, right ventricular failure and death.[2]. Bosentan is an orally active, selective and competitive non-peptide dual endothelin receptor (both ETA and ETB) antagonist and usually used in cure of PAH.[5] Bosentan is being considered for treatment of other conditions such as Eisenmenger syndrome,[6] persistent pulmonary hypertension of the newborn,[7] digital ulcer prevention in patients with systemic sclerosis,[8] adolescent and adult patients who have undergone Fontan operation,[9] vascular remodeling and dysfunctional angiogenesis in diabetes[10] and possibly even depression.[11]

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