PURPOSE: Engineering of inhalation particles incorporating, in each individual particle, a combination of a long-acting beta-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 beta-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 microm. 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.
- Administration, Inhalation
- Adrenal Cortex Hormones
- Adrenergic beta-Agonists
- Bronchodilator Agents
- Calorimetry, Differential Scanning
- Drug Combinations
- Drug Storage
- Microscopy, Electron, Scanning
- Particle Size
- Protein Engineering