title: Surfactant design for the 1,1,1,2-tetrafluoroethane-water interface: ab initio calculations and in situ high-pressure tensiometry.
abstract: 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(b)) 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.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.
authors.affiliation: Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan 48202, USA.
authors.forename: Parthiban
authors.initials: P
authors.lastname: Selvam
authors.forename: Robson P S
authors.initials: RP
authors.lastname: Peguin
authors.forename: Udayan
authors.initials: U
authors.lastname: Chokshi
authors.forename: Sandro R P
authors.initials: SR
authors.lastname: da Rocha
mesh_terms: D003198:Computer Simulation; D005466:Fluorocarbons / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011312:Pressure; D013501:Surface-Active Agents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*; D010420:Pentanes; D004980:Ethane / Q000031:analogs & derivatives
chemical_list: D005466:Fluorocarbons; D006845:Hydrocarbons, Fluorinated; D013501:Surface-Active Agents; D014867:Water; C008806:perfluoropentane; D010420:Pentanes; C063006:norflurane; D004980:Ethane