The influence of relative humidity on particulate interactions in carrier-based dry powder inhaler formulations

Characterisation of dry powder inhaler formulations using atomic force microscopy

“…Thus, the surface of the model carrier was covered by an additional hydrophobic layer which reduced the adhesion between carrier and API particles. A similar impact was also observed for lactose and beclomethasone dipropionate particles (Young et al, 2002). Recent studies by Islam et al (2014) demonstrated the use of a salbutamol sulphate-coated model colloidal probe for comparing the adhesion between hydrophilichydrophilic and hydrophilic-hydrophobic surfaces.…”

“…Sindel and Zimmermann (2001) for example demonstrated the deformation occurring to colloidal lactose probes when pressing them onto a lactose substrate. However, despite investigation, quantifying the impact of surface roughness and surface deformation on the force of adhesion has remained almost impossible (Cline and Dalby, 2002;Louey et al, 2001;Price et al, 2002). The accuracy of the force measurements may therefore be significantly reduced.…”

“…3) to evaluate both the cohesive and adhesive interactions between materials used in drug delivery (Adi et al, 2007;Beilmann et al, 2007;De Boer et al, 2003a,b;Eve et al, 2002;James et al, 2008;Karner et al, 2014;Louey et al, 2001;Price et al, 2002;Sindel and Zimmermann, 2001;Tsukada et al, 2004;Young et al, 2009) and, quite recently, the mechanism of particle detachment (Cui and Sommerfeld, 2015). While three different scenarios describing the process of particle detachment-lift-off, sliding and rolling-are possible, a combination of colloidal probe measurements, simulations and computational modelling identified the rolling mechanism, closely followed by sliding, as the main mechanisms of particle detachment.…”

“…This irregular result may be due to the decay of long-range electrostatic forces at high RH. It was shown (Price et al, 2002) that the significance of capillary forces at a given RH are dependent on the properties of the API. For a budesonide-lactose combination, capillary forces affect the interparticulate forces strongly below 60% RH, while for salbutamol sulphate-lactose blends they only become dominant above 60% RH.…”

Force measurements with the atomic force microscope: Technique, interpretation and applications

“…Due to the significant impact of meniscus forces on the flow behavior of powders, several studies have focused on the humidity dependence of adhesion for several commercially relevant powders like hydrated alumina, a silica aerogel, limestone, titania and zeolite [702] or pharmaceutical products like a-lactose monohydrate, salbutamol sulphate, budesonide, triamcinolone acetonide, and disodium cromoglycate [634,703,704]. Duong et al [705] used force-distance curves on 900-1100 mm glass beads that were exposed to different amount of water in a shaker.…”