Measurement and correlation of solute solubility in HFA-134a/ethanol systems

Julie A. Hoye, Paul B. Myrdal

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


The goals of this study were to determine the solubility values of solid organic solutes in pure HFA-134a and in HFA-134a/ethanol cosolvent systems (0-20%, w/w), and to investigate the relationship between these solubilities and a solute's physico-chemical properties. A direct inject on-line HPLC method was used to determine the solubility of 21 solutes in HFA-134a/ethanol. The samples were allowed to equilibrate for at least 48 h. The filtered sample was injected directly on an analytical HPLC column through a manual injector interface, and analyzed at an appropriate solute wavelength via HPLC. The solutes display diverse physico-chemical properties and yielded solubility values that ranged over four orders of magnitude. In general, a linear-linear solubility relationship was observed as the fraction of ethanol increased. The effects on solubilization ranged from 1.3 to 99.4 times when 20% (w/w) ethanol was introduced, relative to pure HFA-134a. A regression equation utilizing a solute's hydrogen bonding potential resulted in a significant correlation to the slope obtained from a linear model for solubility in HFA-134a with 0-20% (w/w) ethanol, and may be useful for pre-formulation studies.

Original languageEnglish (US)
Pages (from-to)184-188
Number of pages5
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - Oct 1 2008


  • Ethanol
  • HFA-134a
  • MDI
  • Physico-chemical properties
  • Solubility

ASJC Scopus subject areas

  • Pharmaceutical Science


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