PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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