Stabilized terbutaline submicron drug aerosol for deep lungs deposition: drug assay, pulmonokinetics and biodistribution by UHPLC/ESI-q-TOF-MS method

Abstract

Terbutaline submicron particles (SμTBS) were prepared by nanoprecipitation technique followed by spray drying for deep lungs deposition. Inhalable SμTBS particles were 645.16 nm of diameter with 0.11μm of MMAD, suggested for better aerosol effects. Both submicron and micron-sized TBS particles were administered in rodents administered via major delivery routes, and their biological effects were compared by using UHPLC/ESI-q-TOF-MS method. TBS was found stable in all exposed conditions with 96.28-99.0% of recovery and <4.34% of accuracy (CV). An inhalation device was designed and validated to deliver medicines to lungs, which was found best at dose level of 25mg for 30 min of fluidization. Both submicron and micron particles were compared for in vivo lung deposition and a 1.67 fold increase in concentration was observed for SμTBS exposed by inhalation. Optimized DPI formulation contained lesser fraction of ultrafine particle (<500 nm) with the major fraction of submicron particles (>500 nm), advocated for better targeting to lungs. UHPLC/ESI-q-TOF-MS confirmed that designed submicron particles has been successfully delivered to the lungs. From tongue to lungs, the landing of pulmonary medicines can be improved by submicronization technology.