Solubility and precipitation of nicotinic acid in supercritical carbon dioxide.
Solubilities of a model compound (nicotinic acid) in pure supercritical carbon dioxide (SC-CO(2)) and SC-CO(2) modified with methanol have been measured in the pressure range of 80-200 bar and between temperatures of 35 and 90 degrees C. On-line ultraviolet detection enabled a simple and relatively fast measurement of very low levels of solubility (10(-7) mol fraction) with good accuracy in pure and modified SC-CO(2). The solute solubility in both pure SC-CO(2) and SC-CO(2) modified 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 define optimum operating conditions to obtain crystalline particles 1-5 microm in diameter using the solution-enhanced dispersion by supercritical fluids (SEDS) process, thereby demonstrating the feasibility of a one-step production process for particulate pharmaceuticals suitable for respiratory drug delivery.
Rehman
M
M
Drug Delivery Group, School of Pharmacy, University of Bradford, Bradford, BD7 1DP, United Kingdom.
Shekunov
B Y
BY
York
P
P
Colthorpe
P
P
D000535:Aluminum / Q000737:chemistry; D002245:Carbon Dioxide / Q000737:chemistry*; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009525:Niacin / Q000737:chemistry*; D010316:Particle Size; D011208:Powders / Q000032:analysis; D011312:Pressure; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D014961:X-Ray Diffraction
D004337:Drug Carriers; D011208:Powders; D012997:Solvents; D002245:Carbon Dioxide; D009525:Niacin; D000535:Aluminum; D000432:Methanol