Pressurized metered dose inhalers (pMDIs) are the most common vehicles for the delivery of drugs to the lungs, accounting for approximately 80 % of the total prescribed aerosols. However, the development of pMDI-based formulations has been confronted with several challenges since the replacement of CFCs with the more environmentally friendly hydrofluoroalkanes (HFAs). In spite of the fact that the operation of pMDIs with HFAs is similar to those containing CFCs, previous formulations are not compatible due to the significantly different physicochemical properties between these two classes of fluids. Importantly, the amphiphiles in FDA-approved formulations have very limited solubility in 1,1,1,2-tetrafluoroethane (HFA134a) and (1,1,1,2,3,3,3-heptafluoropropane) HFA227. Surfactants are generally required excipients in pMDIs, with functions including dispersion stabilization and valve lubrication. Today's formulations incorporate co-solvents (alcohols) in order to enhance the solubility of the amphiphiles. However, co-solvents may negatively impact the formulations, decreasing their chemical and/or physical stability.

In this work, triblock copolymers of the type polylactide-poly(ethylene glycol)-polylactide (LAmEOnLAm) with various molecular weight and % EO were synthesized and characterized by 1H-NMR. Colloidal Probe Microscopy (CPM) was utilized to determine the cohesive forces of a polar drug in a model propellant (2H,3H-perfluoropentane, HPFP) in presence of the synthesized amphiphiles. The CPM results were compared and contrasted to the bulk physical stability (visual observations) of the dispersions in HPFP and in situ in 1,1,1,2,3,3,3-heptafluoropropane (HFA227). Scanning electron (SEM) and optical microscopy were utilized to characterize the morphology and size of the drug particles. The LAmEOnLAm surfactants are shown to provide long term physical stability to the dispersions in both HPFP and HFA227, with creaming rates on the order of hours. These results compare very favorably to a formulation containing oleic acid and ethanol, and that with a non-ionic triblock copolymer with the propylene oxide moiety as the HFA-phile. CPM results show that the overall concentration, molecular weight, surfactant tail (LA) length, and the ratio between the stabilizing LA moiety and the anchor EO group have a great influence on the cohesive forces between salbutamol particles. The applicability of LA-based amphiphiles might be extended to other suspension-based formulations, provided a suitable head-groups are selected.