Surface energy changes and their relationship with the dispersibility of salmeterol xinafoate powders for inhalation after storage at high RH.

This study investigated the relationship between surface energy of micronized lactose, coarse lactose and salmeterol xinafoate and dispersibility from a mixture after storage at 75% RH. Surface energies, dispersibility, morphology, and the presence of amorphous domains were determined by inverse gas chromatography, twin stage impinger, scanning electron microscope and dynamic vapour sorption, respectively. The fine particle fraction of mixture decreased significantly in 4 weeks (P<0.05), reaching a static level in 3 months. Amorphous content was not detected in the micronized lactose, coarse lactose and salmeterol xinafoate. After conditioning stored samples at 75% RH for 2h, dispersive surface energy of both micronized and coarse lactose significantly decreased (P<0.05), while the polar surface energy of all significantly increased (P<0.05) resulting in significant increase in total surface energy after storage. After conditioning stored samples at 0% RH for 2h, no significant difference was observed in any surface energy parameter. This study concluded that the total surface energy increased during storage at high RH due to the adhered surface moisture. The mechanism of decreased dispersibility was related to increased capillary/solid bridging interactions and to possible increased interaction of contiguous particles due to increased polar surface energy.