Gas antisolvent recrystallization of an organic compound. Tailoring product PSD and scaling-up

An organic pharmaceutical compound has been precipitated from an ethanol solution using dense carbon dioxide as antisolvent. The goals are to analyze the effect of two process parameters, namely antisolvent addition rate and initial solute concentration, on product quality, and to verify the possibility of scaling-up the process. The average particle size of the amorphous product could be reproducibly adjusted in a range spanning more than one order of magnitude from 0.36 to 8.1 μm by changing the specific carbon dioxide addition rate over about two orders of magnitude. The particle size distribution was unimodal and narrow for low and high specific antisolvent addition rates, and it was bimodal for intermediate ones. The results obtained in experiments carried out in a 1-l precipitator are qualitatively and quantitatively the same as those obtained in a 300-ml precipitator, and reported previously (Ind. Eng. Chem. Res. 39 (2000) 2260), thus demonstrating the possibility of scaling-up the gas antisolvent recrystallization process. Changing the initial solute concentration at constant antisolvent addition rate yields populations of particles, whose particle size distributions are qualitatively identical and quantitatively not very different. This shows that contrary to antisolvent addition rate, initial solute concentration cannot be used effectively to adjust the final product quality.