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Drug delivery to the body via the inhaled route is dependent upon patient status, device use, and respirable formulation characteristics. Further to inhalation, drug-containing particles interact and dissolve within pulmonary fluid leading to the desired pharmacological response. Pulmonary surfactant stabilises the alveolar air-liquid interface and permits optimal respiratory mechanics. This material represents the initial contacting surface for all inhaled matter. On dissolution, the fate of a drug substance can include receptor activation, membrane partitioning and cellular penetration.Here, we consider the partitioning behaviour of salbutamol when located in proximity to a simulated pulmonary surfactant monolayer at pH 7. The administration of salbutamol to the underside of the surfactant film resulted in an expanded character for the 2-dimensional ensemble and a decrease in the compressibility term. The rate of drug partitioning was greater when the monolayer was in the expanded state (ie, inhalation end-point), which was ascribed to more accessible areas for molecular insertion. Quantum mechanics protocols, executed via Gaussian 09, indicated that constructive interactions between salbutamol and integral components of the model surfactant film took the form of electrostatic and hydrophobic associations. The favourable interactions are thought to promote drug insertion into the monolayer structure leading to the observed expanded character. The data presented herein confirm that drug partitioning into pulmonary surfactant monolayers is a likely prospect further to the inhalation of respirable formulations. As such, this process holds potential to reduce drug-receptor activation and/or increase the residence time of drug within the pulmonary space.