Engineering of Crystalline Combination Inhalation Particles of a Long-Acting β2-agonist and a Corticosteroid

Purpose Engineering of inhalation particles incorporating, in each individual particle, a combination of a long-acting β-agonist and a glucocorticosteroid in a pre-determined and constant ratio for delivery via a dry powder inhaler (DPI). Methods Individual crystalline particles containing both the glucocorticosteroid fluticasone propionate (FP) and long-acting β-agonist salmeterol (SX) were prepared, in a ratio of 10:1, using the solution atomization and crystallization by sonication (SAX) process. Combination drug particles were characterized by particle size, morphology, crystallinity and aerosolisation efficiency using inertial impaction. Results Combination drug particles were spherical and crystalline, with a median diameter of 4.68 ± 0.01 μm. Aerosolisation of formulations containing combination drug particles resulted in greater uniformity in delivery ratios of both actives across all stages of the impactor before and after storage. Conclusions Actives in a pre-determined dose ratio can be crystallised in a single particle using the SAX process.