• chemical force microscopy;
  • ethanol;
  • hydrofluoroalkanes;
  • pressurized metered-dose inhalers;
  • Johnson-Kendall-Roberts theory


Objectives  The goal of this work was to evaluate the ability of ethanol mixed with hydrofluoroalkanes (HFAs) to improve solvation of moieties of relevance to pressurized metered-dose inhalers (pMDIs).

Methods  Chemical force microscopy was used to measure the adhesion force (Fad) between alkyl-based, ether-based and ester-based moieties (C8/C8, COC/COC and COOC/COOC interactions) in 2H,3H-perfluoropentane (HPFP)/ethanol mixtures. HPFP is a liquid that mimics propellant HFAs. The Fad results are thus a measure of solvation in HFAs. Johnson–Kendall–Roberts (JKR) theory was used to model the results.

Key findings  The Fad normalized by the tip radius of curvature (Fad/R) decreased upon the addition of ethanol, suggesting its ability to enhance the solvent environment. At 15% (v/v) ethanol, the Fad/R was reduced 34% for the alkyl, 63% for the ether, and down 67% for the ester tails. Thus, the solvation could be ranked as: ester > ether > alkyl. JKR theory was a reasonable model for the Fad/R.

Conclusions  Ethanol, within the concentration range of interest in commercial pMDIs, provided limited enhancement in solvation of alkyl moieties. On the other hand, the cosolvent significantly enhanced solvation of ether-based and ester-based moieties, thus suggesting its potential for formulations containing amphiphiles with such groups.