(462a) Biocompatible Surfactants for the Hydrofluoroalkane|Water Interface

Aqueous reverse aggregates in hydrofluoroalkanes (HFAs) can be used for the delivery of both small polar solutes and biomolecules to and through the lungs using pressurized metered-dose inhalers (pMDIs). Interfacially active species at the HFA|Water (HFA|W) interface are required to form and stabilize such aggregates. However, the methyl-based FDA approved surfactants for pMDIs have extremely low solubility in HFAs, and cannot stabilize water-in-HFA (W/HFA) microemulsions. The low solubility of these amphiphiles has been attributed to the poor solvation of the hydrogenated tails by the semi-fluorinated propellants. Understanding the relationship between the chemistry of candidate surfactant tail moieties to their HFA-philicity, and surfactant balance at the HFA|W interface is of great relevance for the development of such formulations. However, very little work has been done at the HFA|W interface, mostly due to difficulties in studying the interfacial properties and micellization behavior in situ (under pressure).

In this work, we investigate the interfacial activity of biocompatible nonionic block copolymer surfactants at the HFA|W interface. A series of amphiphiles containing a biodegradable HFA-phile, with varying molecular weight and percentages of the hydrophile-to-HFA-phile (HFB), have been synthesized. The fundamental interfacial properties of these surfactants, including interfacial tension and micellization behavior, have been determined in situ, under pressure. This new class of amphiphiles is shown to be more interfacially active than both alkyl (including FDA approved surfactants) and ether-based surfactants. Tension reduction of as much as 30 mN/m was observed. An increase in the number of repeat units of the HFA-philic moiety is shown to cause further increase in interfacial activity, bringing the overall tension value close to zero. Spontaneous emulsification is observed with certain surfactants. These amphiphiles are shown to form aggregates in HFAs in the presence of water. Both critical aggregation concentration (c.a.c) and adsorbed amounts were determined. This work is also relevant for existing solution and dispersion-based pMDIs, vehicles that also require the use of surfactants for their optimum formulation.