The formulation of a pressurised metered dose inhaler containing theophylline for inhalation.

Background: Theophylline (TP) is a bronchodilator used orally to treat Chronic Obstructive Pulmonary Disease (COPD) that has been associated with multiple side effects, tempering its present use. This study aims to improve COPD treatment by creating a low-dose pressurized Metered Dose (pMDI) inhalable formulation of TP.

Methods: Aerosol performance was assessed using Andersen Cascade Impaction (ACI). Solubility of TP in HFA134/ethanol mixture was measured and morphology of the particles analyzed with a Scanning Electron Microscope (SEM). Calu-3 cell viability, epithelial cell transport and inflammatory-response assays were conducted to study the impact of the formulation on lung epithelial cells.

Results: The mass deposition profile of the formulation showed an emitted dose of 250.04 ± 14.48 µg per 5 actuations, achieving the designed nominal dose (50µg/dose). SEM showed that the emitted particles were hollow with spherical morphology. Approximately 98% of TP was transported across Calu-3 epithelial cells and the concentration of interleukin-8 secreted from Calu-3 cells following stimulation with tissue necrosis factor-α (TNF-α) resulted in significantly lower level of interleukin-8 released from the cells pre-treated with TP (1.92 ± 0.77 ng.ml-1 TP treated vs. 8.83 ± 2.05 ng.ml-1 TNF-α stimulated, respectively).

Conclusions: The solution pMDI formulation of TP developed in present study was shown to be suitable for inhalation and demonstrated anti-inflammatory effects at low doses in Calu-3 cell model.