Morphology and growth control of griseofulvin recrystallized by compressed carbon dioxide as antisolvent

Griseofulvin has been crystallized from acetone solutions using compressed carbon dioxide as antisolvent. Crystallization was performed in a batch stirred vessel at a temperature of 40degreesC and a final pressure of 100 bar. The effects of the antisolvent addition rate and of the stirring rate upon the morphology and size of the precipitated crystals were particularly investigated. Parameters were varied between 1. 3-5.6 bar/min and 33-1000 rpm, respectively. Over the whole set of conditions, the product was obtained as tetragonal crystals with mean sizes from 40 mum to 20 mm. For a given CO2 addition rate, the crystal morphology switched from a long needle to a bipyramid form as the stirring rate increased. For a given stirring rate and a given morphology, size of crystals decreased as the CO2 addition rate increased. The rates also influenced the particle size distribution. The smallest size and narrowest particle size distribution were obtained at the highest stirring rate and antisolvent introduction rate, i.e. 1000 rpm and 5.6 bar/min, respectively. (C) 2003 Elsevier B.V. All rights reserved.