Surfactant Design for the 1,1,1,2-Tetrafluoroethane-Water Interface:ab initio Calculations and in situ High-Pressure Tensiometry

摘要

In situ high-pressure tensiometry and ab initio calculations were used to rationally design surfactants for the 1,1,1,2-tetrafluoroethane-water (HFA134a|W) interface.Nonbonded pair interaction (binding) energies (E_bb) of the complexes between HFA134a and candidate surfactant tails were used to quantify the HFA-philicity of selected moieties.The interaction between HFA134a and an ether-based tail was shown to be predominantly electrostatic in nature and much more favorable than that between HFA134a and a methyl-based fragment.The interfacial activity of (i) amphiphiles typically found in FDA-approved pressurized metered-dose inhaler (pMDI) formulations,(ii) a series of nonionic surfactants with methylene-based tails,and (iii) a series of nonionic surfactants with ether-based tails was investigated at the HFA134a|W interface using in situ tensiometry.This is the first time that the tension of the surfactant-modified HFA134a|W interface has been reported in the literature.The ether-based surfactants were shown to be very interfacially active,with tension decreasing by as much as 27 mN centre dot m~(-1).However,the methyl-based surfactants,including those from FDA-approved formulations,did not exhibit high activity at the HFA134a| W interface.These results are in direct agreement with the E_b calculations.Significant differences in interfacial activity are noted for surfactants at the 2H,3H-perfluoropentane (HPFP)|water and HFA134a|W interfaces.Care should be taken,therefore,when results from the mimicking solvent (HPFP) are extrapolated to HFA134a-based systems.The results shown here are of relevance in the selection of surfactants capable of forming and stabilizing reverse aqueous aggregates in HFA-based pMDIs,which are promising formulations for the systemic delivery of biomolecules to and through the lungs.