Solubility and precipitation of nicotinic acid in supercritical carbon dioxide

✍ Scribed by M. Rehman; B. Y. Shekunov; P. York; P. Colthorpe

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 327 KB
• Volume: 90
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1107

✦ Synopsis

Solubilities of a model compound (nicotinic acid) in pure supercritical carbon dioxide (SC-CO 2 ) and SC-CO 2 modi®ed with methanol have been measured in the pressure range of 80±200 bar and between temperatures of 35 and 908C. On-line ultraviolet detection enabled a simple and relatively fast measurement of very low levels of solubility (10 À7 mol fraction) with good accuracy in pure and modi®ed SC-CO 2 . The solute solubility in both pure SC-CO 2 and SC-CO 2 modi®ed with methanol increased with pressure at all investigated temperatures. A retrograde solubility behavior was observed in that, at pressures below 120 bar, a solubility decrease on temperature increase occurred. Solubility data were used to calculate supersaturation values and to de®ne optimum operating conditions to obtain crystalline particles 1±5 mm in diameter using the solution-enhanced dispersion by supercritical ¯uids (SEDS TM ) process, thereby demonstrating the feasibility of a one-step production process for particulate pharmaceuticals suitable for respiratory drug delivery.