Preparation of Dry Powder Inhaler of Montelukast Sodium-Loaded Solid Lipid Nanoparticles and Evaluation of its Physicochemical Characteristics

Abstract

The aim of the current study was to formulate montelukast sodium into solid lipid nanoparticles (SLNs) for pulmonary application to improve its systemic bioavailability, to reduce the metabolite-based hepatic cellular toxicity and to avoid the hepatic metabolism. Montelukast loaded SLNs were prepared using hot homogenization method while its dry powder inhaler (DPI) was made by spray drying method without and with 4% mannitol and lactose as carrier. The Carr's index and Hausner ratio were calculated as appropriate criteria for the evaluation of the DPIs flowability. In vitro deposition of the aerosolized drug was studied using a Next Generation Impactor (NGI) at 60 L/min following the methodology described in the European and United States Pharmacopeias. The particle size and encapsulation efficiency (EE) of montelukast loaded SLNs were below 100 nm and > 99%, respectively. In vitro aerosol performance study indicated more than 93% of the emitted dose (ED) for DPIs containing mannitol and lactose as carrier in comparison with 78% for DPI prepared without any sugars. The fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of all prepared powders were reasonable enough for DPIs. The attained results indicate that this novel inhalable spray dried nanoparticulates mounted on microparticles aerosol platform may offer improved systemic delivery of the montelukast sodium.