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

An atomic force microscope (AFM) colloid probe technique has been used to investigate the effect of relative humidity (RH) on the adhesion properties of pharmaceutical powder surfaces. The adhesion between a model substrate, alpha-lactose monohydrate, and model particulate drugs, salbutamol sulphate and budesonide, was investigated between RHs of 15 and 75%. The surface topography of the model alpha-lactose monohydrate was produced by controlling the supersaturation conditions during crystal growth to produce sub-nanometre scale roughness. The adhesion interactions between lactose and drug probes of salbutamol sulphate and budesonide were shown to be significantly increased with each incremental rise in humidity. Capillary forces were significantly more dominant for the adhesion in the budesonide-lactose system up to 60% RH but were more dominant for salbutamol sulphate-lactose above 60% RH. These studies suggested that non-surface-specific capillary forces play a dominant role in the adhesion between drug and carrier, which may significantly reduce the deaggregation and dispersion properties of a dry powder formulation.