Solubility and precipitation of nicotinic acid in supercritical carbon dioxide

Solubilities of a model compound (nicotinic acid) in pure supercritical car bon dioxide (SC-CO2) and SC-CO2 modified with methanol have been measured i n the pressure range of 80-200 bar and between temperatures of 35 and 90 de greesC. On-line ultraviolet detection enabled a simple and relatively fast measurement of very low levels of solubility (10(-7) mol fraction) with goo d accuracy in pure and modified SC-CO2. The solute solubility in both pure SC-CO2 and SC-CO2 modified with methanol increased with pressure at all inv estigated temperatures. A retrograde solubility behavior was observed in th at, at pressures below 120 bar, a solubility decrease on temperature increa se occurred. Solubility data were used to calculate supersaturation values and to define optimum operating conditions to obtain crystalline particles 1-5 mum in diameter using the solution-enhanced dispersion by supercritical fluids (SEDS (TM)) process, thereby demonstrating the feasibility of a one -step production process for particulate pharmaceuticals suitable for respi ratory drug delivery. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceut ical Association.