(638e) Reverse Perfluorocarbon Emulsions for Pulmonary Drug Delivery: Effects of Emulsion Formulation on Drug Mass Transfer

Pulmonary drug delivery using water-in-perfluorocarbon reverse emulsions has the potential to improve traditional treatment methods of lung diseases. Liquid perfluorocarbons (PFC) function like air, providing a medium for gas exchange; and as a delivery vehicle, enabling deeper lung penetration of delivered drugs. Since most drugs are sparingly soluble in PFC liquids, aqueous drug solutions must be dispersed as a water/PFC emulsion. Several studies have confirmed drug-loaded PFC emulsions maintain therapeutic effects; however, few studies have engineered controlled release profiles that cater to specific therapeutic windows or disease states. This study concerns the effects of emulsion formulation on drug mass transfer into an aqueous receiving phase with particular emphasis on the role of emulsion droplet coalescence with the aqueous receiving phase, and its dependence on fluorosurfactant concentration.

Water/PFC emulsions were prepared via sonication with constant antibiotic concentration in the dispersed aqueous phase and varying fluorosurfactant concentrations. The emulsion was dispensed into a cylindrical well within inoculated agar to monitor delivery of emulsified antibiotic over 24 hours. Antibiotic delivery peaked at 55% with an intermediate fluorosurfactant concentration. Lower fluorosurfactant concentrations failed to sufficiently encapsulate antibiotic and, thus, had less drug delivery. Higher fluorosurfactant concentrations also had less drug delivery, suggesting either aqueous droplets are unable to freely diffuse into the agar or the diffusional capability of the drug is hindered.

This phenomenon was further explored using fluorescein as a drug mimic. Water/PFC emulsions were prepared via sonication with constant fluorescein concentration in the dispersed aqueous phase, varying water:PFC volume ratios and varying fluorosurfactant concentrations. The emulsion was quiescently contacted with a saline receiving phase in a cuvette to monitor fluorescein uptake over 72 h. Less than 60% of the fluorescein was transferred to the saline phase over 72 h. Mass transfer rates were strongly correlated with fluorosurfactant concentration and the fluorosurfactant:water ratio in a manner suggesting that the rate of aqueous emulsion droplet coalescence with the receiving phase was rate determining, rather than mass transfer through the continuous PFC phase. For a given fluorosurfactant concentration, the droplets with the highest drug concentration (lowest aqueous volume percent) had the lowest mass transfer.

Thus, experiments were conducted to measure coalescence times for individual aqueous droplets placed at a saline-PFC interface. Coalescence rates were also strongly correlated with fluorosurfactant concentration, primarily via the fluorosurfactant effect on the stability of the thin PFC film separating the drop from the bulk saline phase.

Work is ongoing to fully map the correlations between emulsion formulation, stability, fluorescein mass transfer and droplet/receiving phase coalescence rate, including the specific effects of the type of PFC and fluorosurfactant.