Carrier free dry powder formulation of sildenafil for potential application in pulmonary arterial hypertension

Abstract

The present study was designed to prepare sildenafil carrier free dry powder inhalation (DPI) formulation for the treatment of idiopathic pulmonary arterial hypertension (IPAH). Sildenafil DPI formulations were fabricated by spray drying technique. The ideal formulation was optimized using different solvent type (methanol, dimethylformamide and water), concentration (5 and 50 mg/mL) and pH (2 and 7.4) of feed solution. Particles size distribution, morphology and crystallinity of fabricated microparticles were evaluated by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) methods, respectively. The aerosolization efficiency of formulations were assessed by next generation impactor equipped with an Aerolizer (R). Results indicated that evaluated variables had great impacts on powder characteristics which significantly influenced aerosolization performance of formulations. The aerosolized fraction of formulations was improved from 2 to 70 % by changing in solvent type and drug concentration in spray dryer feeding solution. Aerosolization performance of powders were well correlated and interpreted by their morphologies as depicted from SEM images. DSC results also indicated that crystallinity of all formulations were reduced by spray drying procedure. Optimization of spray drying technique for production of Sildenafil carrier free DPI formulation in this study may pave a way for locally treatment of IPAH.