Leucine enhances the dispersibility of trehalose-containing spray-dried powders on exposure to a high-humidity environment

Abstract

This study investigates the ability of various shell-forming excipients to preserve the dispersibility of dry powder dosage forms, e.g., nasally administered vaccines, upon exposure to a high-humidity environment. Trehalose combinations using leucine, pullulan, or trileucine were selected as the candidate excipient systems, and the powder dispersibility of these systems was compared with that of pure trehalose particles. Scaled-up monodisperse spray drying was used to produce sufficient quantities of uniform-sized particles for powder dispersibility analysis. Particle size, crystallinity, and morphology of the powders before and after exposure to moisture were characterized by an aerodynamic particle sizer, Raman spectroscopy, and scanning electron microscopy, respectively. Three two-component particle systems composed of trehalose/trileucine (97/3 w/w), trehalose/pullulan (70/30 w/w), and trehalose/leucine (70/30 w/w) were first formulated and their dispersibility, characterized as the emitted dose from dry powder inhalers, was then compared with that of trehalose particles. The formulation containing 30% leucine maintained the highest emitted dose (90.3 ± 10%) at a 60 L/min flow rate after 60 min exposure to 90% RH and 25 °C, showing its superior protection against exposure to humidity compared with the other systems. Further investigations under more challenging conditions at a 15 L/min flow rate on the trehalose/leucine system with various compositions (70/30, 80/20, 90/10 w/w) showed that a higher leucine concentration generally provided better protection against moisture and maintained higher powder dispersibility, probably due to higher surface coverage of crystalline leucine and a thicker leucine shell around the particle. The study concludes that leucine may be considered an appropriate shell-forming excipient in the development of dry powder formulations in order to protect the dosage forms against humidity during administration.