Concurrent oral and inhalation drug delivery using a dual formulation system: the use of oral theophylline carrier with combined inhalable budesonide and terbutaline

A novel approach to concurrently deliver oral and inhaled drugs as a single formulation is presented. A triple therapy containing theophylline (THEO; orally delivered) with budesonide (BUD) and terbutaline (TERB) (as single and co-spray dried inhaled powders) were prepared as an ordered mix, with THEO acting as a carrier. The aerosolisation performance of THEO formulations containing BUD and TERB alone, physical mix and co-spray dried powder were evaluated using a next generation impactor (NGI). Physico-chemical properties were investigated using electron microscopy, laser diffraction, dynamic vapour sorption and thermal analysis. NGI analysis indicated that >99% of the THEO powder was greater than 4.46 mm, with >90% dissolved within 5 minutes. Particle size analysis showed samples suitable size for inhalation. Thermal and moisture analysis suggested powders to be stable at room temperature up to 70% RH. Aerosol studies indicated different performance of BUD and TERB depending on the mixing procedure. The co-spray dried formulation showed the highest performance, with a fine particle fraction (≤4.46 microns) of BUD and TERB of 34.39 ± 3.56 % and 33.61 ± 5.67 %, respectively. Such observations suggest this multicomponent drug delivery system could be developed to concomitantly deliver oral and inhaled drugs, an approach that, to date does not exist. Ultimately, this technology potentially reduces the requirement for multiple therapies and increases patient compliance.