P-185 An inhalation safety study of myoinositol, a non-hygroscopic stabilizing excipient in dispersible microparticles

Myo-inositol is an effective, non-hygroscopic replacement for sorbitol in the re-formulation of live attenuated measles vaccine as a dispersible dry powder for pulmonary delivery. Myo-inositol, a six-carbon cyclic polyol commonly found in animals and plants, commercially derived from rice, is not presently on regulatory agency lists of approved inhalable excipients. Myo-inositol produces comparable inhalable microparticles to the currently approved inhalable sugar excipients (mannitol and lactose) but exhibits superior stabilization and non-hygroscopicity. Formulations of a dry powder measles vaccine containing myo-inositol as a primary constituent have been delivered by inhalation to Rhesus macaques with no adverse effects. Myo-inositol and a lactose control were formulated with 1.5% leucine and processed into dry powders by CAN-BD for use in a GLP toxicology study in rats. Study parameters included clinical, ophthalmologic, and cageside observations, organ weights, clinical pathology and histopathology. The aerosolized micropartides were delivered to Sprague Dawley rats via at-liberty breathing using a BD Solovent DPI. Doses of the myo-inositol-containing powders, up to 30 mg/day for 3 consecutive days (significantly above the proposed human dose), were non-toxic and well tolerated, indicating myo-inositol will be a safe alternative to the currently approved excipients for inhalation. Human Phase I clinical trials are planned.