The purpose of this work is to study the effect of urea as an additive for the habit modification of sulfathiazole (STZ) crystals formed using supercritical antisolvent (SAS) precipitation. The process was performed using acetone and carbon dioxide as solvent and antisolvent, respectively. The effect of STZ concentration, urea concentration, temperature, and pressure on the crystals habit was investigated, and the obtained products were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Urea was found to be very effective in the modification of the crystal habit and size of STZ crystals. The habit changed from a plate shape to spherical particles with a very narrow particle size distribution at a urea/STZ mass ratio of 1%. Mean particle size ranged between 0.5 and 1 ím depending on the STZ concentration in acetone. XRD and DSC analysis indicated the formation of a form I polymorph among the five known polymorphisms of STZ. Because of rapid precipitation, only partly crystalline particles were observed with respect to the raw material. Despite the use of urea as an additive, no detectable urea residue was found in the crystals, because urea is soluble in carbon dioxide and is effectively removed during the washing step with CO2. It is, thus, concluded that urea is mainly adsorbed on the crystal surface rather than being incorporated into the lattice of the STZ crystals.
Use of urea as habit modifier in supercritical antisolvent micronization of sulfathiazole
CAPUTO, GIUSEPPE;REVERCHON, Ernesto
2007-01-01
Abstract
The purpose of this work is to study the effect of urea as an additive for the habit modification of sulfathiazole (STZ) crystals formed using supercritical antisolvent (SAS) precipitation. The process was performed using acetone and carbon dioxide as solvent and antisolvent, respectively. The effect of STZ concentration, urea concentration, temperature, and pressure on the crystals habit was investigated, and the obtained products were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Urea was found to be very effective in the modification of the crystal habit and size of STZ crystals. The habit changed from a plate shape to spherical particles with a very narrow particle size distribution at a urea/STZ mass ratio of 1%. Mean particle size ranged between 0.5 and 1 ím depending on the STZ concentration in acetone. XRD and DSC analysis indicated the formation of a form I polymorph among the five known polymorphisms of STZ. Because of rapid precipitation, only partly crystalline particles were observed with respect to the raw material. Despite the use of urea as an additive, no detectable urea residue was found in the crystals, because urea is soluble in carbon dioxide and is effectively removed during the washing step with CO2. It is, thus, concluded that urea is mainly adsorbed on the crystal surface rather than being incorporated into the lattice of the STZ crystals.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
