Engineering of crystalline combination inhalation particles of a long-acting beta2-agonist and a corticosteroid.
OBJECTIVE
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.
Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Chonladda
C
Pitchayajittipong
Jagdeep
J
Shur
Robert
R
Price
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000737:chemistry*; D000318:Adrenergic beta-Agonists / Q000737:chemistry*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000737:chemistry; D000730:Androstadienes / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D004338:Drug Combinations; D004356:Drug Storage; D000068298:Fluticasone; D001239:Inhalation; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D015202:Protein Engineering; D000068299:Salmeterol Xinafoate
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D011208:Powders; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol