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) was 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 was evaluated using a next-generation impactor (NGI). Physicochemical properties were investigated using electron microscopy, laser diffraction, dynamic vapour sorption and thermal analysis. NGI analysis indicated that >99 % of the THEO powder was >4.46 μm, with >90 % dissolved within 5 min. Particle size analysis showed TEB and BUD samples were of a suitable size for inhalation. Thermal and moisture analysis suggested powders to be stable at room temperature up to 70 % RH. Aerosol studies indicated a 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 μm) of BUD and TERB of 34.39 ± 3.56 and 33.61 ± 5.67 %, respectively. Such observations suggest that 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.