title: Solvation in hydrofluoroalkanes: How can ethanol help?
abstract: OBJECTIVE
  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 (F(ad)) 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 F(ad) results are thus a measure of solvation in HFAs. Johnson-Kendall-Roberts (JKR) theory was used to model the results.
  
  
  RESULTS
  The F(ad) normalized by the tip radius of curvature (F(ad)/R) decreased upon the addition of ethanol, suggesting its ability to enhance the solvent environment. At 15% (v/v) ethanol, the F(ad)/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 F(ad)/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.
authors.affiliation: Department of Chemical Engineering and Materials Science, College of Engineering, Wayne State University, Detroit, MI, USA.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Conti
authors.forename: Jordan
authors.initials: J
authors.lastname: Grashik
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Libo
authors.initials: L
authors.lastname: Wu
authors.forename: Sandro R P
authors.initials: SR
authors.lastname: da Rocha
mesh_terms: D000268:Adhesiveness; D000280:Administration, Inhalation; D000335:Aerosol Propellants / Q000737:chemistry*; D000473:Alkanes / Q000737:chemistry*; D016503:Drug Delivery Systems; D004952:Esters / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry; D005466:Fluorocarbons / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D036501:Metered Dose Inhalers; D018625:Microscopy, Atomic Force; D008956:Models, Chemical; D009994:Osmolar Concentration; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D013535:Suspensions; D010420:Pentanes
chemical_list: D000335:Aerosol Propellants; D000473:Alkanes; D004952:Esters; D000431:Ethanol; D004987:Ethers; D005466:Fluorocarbons; D006845:Hydrocarbons, Fluorinated; D014677:Pharmaceutical Vehicles; D012997:Solvents; D013501:Surface-Active Agents; D013535:Suspensions; C008806:perfluoropentane; D010420:Pentanes