Agglomerate properties and dispersibility changes of salmeterol xinafoate from powders for inhalation after storage at high relative humidity.
OBJECTIVE
This study investigated changes in agglomeration and the mechanism of dispersibility decrease of salmeterol xinafoate (SX) from SX-lactose mixtures for inhalation after storage at 75% RH for 3 months.


METHODS
The dispersibility, PSD and in situ PSD of aerosol plumes of SX alone and SX-coarse lactose (CL) mixtures containing 0, 5, 10 and 20% micronized lactose (ML) before and after storage were determined by a Next Generation Impactor (NGI), a Mastersizer 2000 and a Spraytec, respectively.


RESULTS
The PSD of ML increased after storage at 75% RH, but dispersibility of SX using the stored ML increased. After storage, the %SX of the mixture containing 20% ML (M20F) significantly increased (P<0.05) in the throat and mouthpiece, preseparator and stage 1 of NGI, while it significantly decreased in the remaining stages (P<0.05). In situ analysis of aerosol plumes of M20F supported this result with an increased presence of particles of 4-25microm and a decreased respirable particle distribution of <4microm after storage.


CONCLUSIONS
The decreased dispersibility of M20F after storage was due to the formation of less dispersible agglomerates, probably occurring through enhanced capillary interaction and/or solid bridging of ML, entrapping and preventing the release of SX particles.
Das
Shyamal
S
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Victoria 3052, Australia.
Larson
Ian
I
Young
Paul
P
Stewart
Peter
P
D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients; D006813:Humidity; D007785:Lactose; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D011312:Pressure; D000068299:Salmeterol Xinafoate
D000336:Aerosols; D001993:Bronchodilator Agents; D005079:Excipients; D011208:Powders; D000068299:Salmeterol Xinafoate; D007785:Lactose; D000420:Albuterol