Measurement and correlation of solute solubility in HFA-134a/ethanol systems.
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.
Hoye
Julie A
JA
CovX Research, 9381 Judicial Dr, San Diego, CA 92122, USA. jhoye@covx.com
Myrdal
Paul B
PB
D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D000431:Ethanol / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D016014:Linear Models; D036501:Metered Dose Inhalers; D012995:Solubility; D005466:Fluorocarbons
D004337:Drug Carriers; D000431:Ethanol; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons