Preparation and characterization of a dry powder inhalation (DPI) containing solid nanoparticles encapsulating amphotericin B

Background and Objective:The aim of this study was to prepare dry powder inhalers (DPIs) containing amphotericin B solid lipid nanoparticles (AMB-SLNs).Preparation of DPI formulations containing solid lipid nanoparticles encapsulating AMB-DSPG complex was studied as an alternative way for prevention of pulmonary aspergillosis.Materials and Methods:For improving the solubility of amphotericin B in organic solvents, ion paired complexes were formed by establishing electrostatic interaction between amphotericin B and distearoyl phosphatidylglycerol (DSPG). The SLN formulations containing AMB-DSPG complexes were prepared using glycerol monostearate (GMS) as the lipid matrix and soybean lecithin and tween 80 as the surfactant by solvent emulsification-evaporation technique. The nanoparticles were optimized through a fractional factorial design. DPIs were prepared by lyophilization technique using lactose as the inhalational carrier and then after, the formulations were evaluated in terms of aerodynamic particle size distribution using a cascade impactor. The morphology of the particles was examined using scanning electron microscopy. The in vitro drug release profiles were evaluated.Findings:The particle size, PdI, zeta potential, entrapment efficiency and drug loading capacity of the optimized SLNs were 187.04±11.97 nm, 0.188±0.028, -30.16±1.6 mV, 89.3±3.47 % and 2.76±0.32 %, respectively. Formulation containing 10%w/v of lactose with the calculated fine particle fraction value as 72.57±4.33 was exhibited the appropriate aerodynamic characteristics for pulmonary drug delivery. SEM images revealed de-agglomerated particles. In vitro release studies showed sustained release of AMB and the release kinetics were best fitted to the first order kinetic model.Conclusions:The results found here indicated that AMB-SLNs could be successfully prepared and stabilized through freeze drying.

Keywords:

Amphotericin B , Ion paired complexation , distearoyl phosphatidylglycerol (DSPG) , Solid lipid nanoparticles (SLN) , Dry Powder Inhalation (DPI)