Abstract
The in vitro dispersion of salmeterol xinafoate (SX) alone and four SX (2.5%)-coarse lactose (CL) mixtures containing 0%, 5%, 10% and 20% micronised lactose (ML) was monitored during 18-month storage at 33%, 55% and 75% relative humidity (RH) using a twin stage impinger. The surface moisture was monitored over 2 months by thermo gravimetric analysis. The morphology was determined by scanning electron microscopy. An aerosizer was used to compare the agglomerate strengths of formulations before and after storage at 75% RH. Upon storage, no significant difference occurred in fine particle fraction (FPF) of any formulation at 33% and 55% RH. Within 8 weeks, the FPF of mixture containing 20% ML (M20F) significantly decreased from 11.3% to 7.7% at 75% RH (p = 0.008) and to 4.9% at 95% RH (p = 0.001). The calculated capillary forces were greater for ML-ML contact than other particle interactions and the propensity of ML-ML contacts was higher in M20F. The agglomerate strength of M20F significantly increased after storage. The study concluded that the critical factors for decreased dispersion of SX formulations were RH of 75% or greater and the presence of high concentrations of ML due to capillary forces and/or solid bridge formation of ML leading to increased agglomerate strength. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1015-1027, 2009