Present address: MAP Pharmaceuticals, Mountain View, CA 94043, USA.
Solvation in hydrofluoroalkanes: how can ethanol help?
Version of Record online: 18 NOV 2011
© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society
Journal of Pharmacy and Pharmacology
Themed Issue: Inhalation Pharmaceutics – Current Technologies and Approaches to Respiratory Drug Delivery. Guest Editors: Paul M. Young and Daniela Traini
Volume 64, Issue 9, pages 1236–1244, September 2012
How to Cite
Conti, D. S., Grashik, J., Yang, L., Wu, L. and da Rocha, S. R. P. (2012), Solvation in hydrofluoroalkanes: how can ethanol help?. Journal of Pharmacy and Pharmacology, 64: 1236–1244. doi: 10.1111/j.2042-7158.2011.01398.x
- Issue online: 6 AUG 2012
- Version of Record online: 18 NOV 2011
- Received August 9, 2011; Accepted October 11, 2011
- chemical force microscopy;
- 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.