The Relationship between the Performance and Surface Energy of Salmeterol Xinafoate Powders for Inhalation during long term Storage at different Relative Humidity
Purpose: This study investigated the relationship between the performance and surface energies of salmeterol xinafoate (SX) powders for inhalation stored over six month at different RH. Methods: Five formulations, SX alone and four SX-coarse lactose (CL) mixtures containing 0%, 5%, 10% and 20% fine lactose (FL), were kept at 33%, 55% and 75% RH. In vitro aerosol deposition (expressed as Fine Particle Fraction - FPF) was determined by a Twin Stage Impinger. Dispersive (γD) and specific surface energies (γSP) at infinite dilution and surface heterogeneity profiles of initial and stored (three months at 75%RH) samples were determined by Inverse Gas Chromatography. Results: The FPF of SX mixture containing 20% FL significantly decreased from 11.3% to 7.7% at 75%RH and to 4.9% at 95%RH within the first 8 weeks. Other formulations showed no significant change in conditions up to 75% RH. The γSP decreased for all samples. The γD of CL and FL decreased, while that of SX increased and that of SX mixture containing 20% FL remained unchanged. Surface heterogeneity profiles showed significant decrease in total energy sites of all samples upon storage. Conclusions: The study concluded that the critical factors for decreased performance of SX formulations were 75% or greater RH and the presence of high concentrations of FL. The reduced performance upon storage at higher humidity coincided with the decrease in the surface energy of the CL and FL in SX formulations.