Olli Aaltonen

The effect of initial drop size on particle size in the supercritical antisolvent precipitation (SAS) technique

The objective of this study was to find the effect of the initial droplet size on the final particle size in the semi-continuous SAS technique. In this technique the solute of interest is first dissolved in a conventional solvent. Particle formation is accomplished by spraying this solution continuously through a nozzle into a chamber containing subcritical or supercritical carbon dioxide. The droplet sizes were calculated from four alternative equations. The theoretical particle sizes were calculated from the calculated droplet sizes assuming that one agglomerated microparticle is produced from each droplet. The theoretical mean particle sizes and the measured particle sizes were compared. The particle formation model was tested with poly(l-lactid acid) (l-PLA) in dichloromethane (DCM) and carbon dioxide. The smallest l-PLA particles were formed by spraying l-PLA/DCM solution into liquid CO2 below 304 K and 8.0 MPa. Under these conditions, the mean agglomerate particle diameter was less than 4 μm. When spraying the solution into supercritical CO2 at 308–323 K and 10–14 MPa, the mean particle size was 8–14 μm. Higher temperatures and pressures increased the mean particle size. The particles were strongly agglomerated at the highest temperature and pressure (333 K and 17 MPa). Recrystallization of l-PLA into small particles is possible below 308 K and 10 MPa using the SAS technique. According to the droplet formation models, the effects of temperature, pressure, CO2 velocity and density, nozzle diameter, interfacial tension between liquid and CO2, and Reynolds and Weber numbers on the droplet size is small. The calculated theoretical particle size agreed reasonably well with the final particle size at the near critical temperature and pressure of CO2. However, the droplet and particle formation models did not explain the observed changes of particle sizes with changes in operating conditions. It is suggested that the initial droplet sizes, formed at the nozzle, do not have an effect on the final particle size.

Enantioselective esterification of ibuprofen in supercritical carbon dioxide by immobilized lipase

The enantioselective esterification of racemic ibuprofen with n-propanol by immobilized Mucor miehel lipase in supercritical carbon dioxide was studied. The enantiomeric excess of the product (eep) was 70 % at 15...20 % conversion. The enantioselectivity was faintly affected by temperature and the concentration of ibuprofen and lipase. The optimum temperature was 45 °C. The initial reaction rate increased with pressure, but enantioselectivity was not affected by pressure changes. The reaction rates in supercritical carbon dioxide at optimized conditions and in n-hexane were similar.

Stereospecific hydrolysis of 3-(4-methoxyphenyl)glycidic ester in supercritical carbon dioxide by immobilized lipase

In the hydrolysis of racemic 3-(4-methoxyphenyl)glycidic acid methyl ester by immobilized Mucor miehel lipase in supercritical CO2 the initial hydrolysis rate of the (2S,3R)-form was faster than the rate of the (2R,3S) -form. The stereoisomeric excess of the (2R,3S)-form reached 87 % at 53 % total conversion level. The water content of the reaction mixture and the initial concentration of the 3-(4-methoxyphenyl) glycidic acid methyl ester had no effect on isomeric purity. The reaction rate in supercritical CO2 was considerably faster than in toluene/water -mixture.

Continuous catalyst-free aromatization of γ-terpinene using air as an oxidant

The dehydrogenation of γ-terpinene was studied under catalyst- and solvent-free reaction conditions using air as an oxidant. The dehydrogenation affords p-cymene in good yields in a continuous flow reaction setup. The initial optimization of the reaction parameters showed that the dehydrogenation is highly dependent on the vapour/liquid phase equilibrium and the availability of oxygen in the vapour phase.