Solubility of solid solutes in HFA-134a with a correlation to physico-chemical properties

Julie A. Hoye, Abhishek Gupta, Paul B. Myrdal

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The reformulation of pressurized metered dose inhalers with HFAs from CFCs has given rise to many solubility challenges. Compounds and excipients previously used in CFCs were observed to have significantly different solubility values in HFA-134a. In this investigation, the solubility values of 36 solid organic solutes in HFA-134a were determined. The set of compounds display diverse physico-chemical properties and yielded solubility values that ranged over 4 orders of magnitude. The experimental solubilities were compared to calculated values obtained from ideal solubility theory as well as from regular solution theory. While the theoretical models did not offer absolute solubility estimations, a clear correlation with the ideal solubility (melting point) was noted. Further consideration utilizing multiple linear regression models afforded correlations based on molecular properties. Regression models, containing melting point and log P (or molar volume) resulted in promising correlations having average absolute errors of 0.43 log units, or a factor of 2.69.

Original languageEnglish (US)
Pages (from-to)198-208
Number of pages11
JournalJournal of pharmaceutical sciences
Issue number1
StatePublished - Jan 2008


  • Aerosol
  • Correlation
  • HFA-134a
  • HPLC
  • Log P
  • MDI
  • Physico-chemical properties
  • Solubility
  • Structure property relationship

ASJC Scopus subject areas

  • Pharmaceutical Science


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