Summary

Pulmonary drug delivery is a useful route of administration for local and systemic therapy. The aim of this work was to develop a sustained formulation for roflumilast. A human serum albumin (HSA)-based nanoparticle formulation was manufactured using a desolvation method. The drug carrier particles were spherical with diameter 130 – 160 nm and zeta potential of – 20 mV when suspended in PBS. The encapsulation efficiency was approximately 20%, and the nanoparticle formulation contained between 4 – 7.7 µg of encapsulated roflumilast per mg of albumin. In order to investigate the effect of proteolytic activity on the degradation of the carrier particles, a trypsin containing dissolution medium with a protease concentration of 0.1 mg/mL was used.  The nanoparticle count rate was found to undergo rapid reduction with 42.7 ± 10.0% intact nanoparticles left within the first 10 minutes of exposure reducing further to ~ 86% reduction in count rate after 40 minutes. The release of the drug was also evaluated, and the release reaches almost 80% by 48 hours. For delivery to the lungs, the nanoparticle suspension was spray-dried with mannitol and the result produce a mannitol-roflumilast microparticle system with a geometric size of ca. 4 µm.

Key Message

The drug roflumilast can be loaded into an albumin-based system and manufactured as microparticles using spray-drying. Administration using the pulmonary route is anticipated to reduce the dose and spare extra-pulmonary exposure, in particular avoiding the gastrointestinal side effects associated with the 500 µg tablet formulation.