Crystal size control of sulfathiazole using high pressure carbon dioxide

The effect of the pressurization method of carbon dioxide on the crystallization behavior and crystal size of sulphathiazole (SUT) was investigated. In the ''stepwise pressurization'' method exceptionally large pillar-like crystals of 2-6 mm were obtained as mainly a scaling on the wall of the crystallizer. In the ''rapid pressurization'' method, crystals with a size one third to half of that obtained in the stepwise method precipitated, indicating the accelerated nucleation rate by the rapid increase of the supersaturation degree with a vigorous bubbling. With the new method of ''two-step pressurization'', in the first step the nucleation is accelerated with a much larger pressure instantly created, and in the second step the growth rate is retarded with the lower pressure. By this method much more fine crystals (from a few tens to several hundred micrometers) were produced and the scaling was suppressed. In this method a large supersaturation degree at an interface between the gas (bubble) and liquid phase under a vigorous bubbling may play an important role in accelerating the nucleation. The average size of the crystals tended to become smaller with increase of the first pressure and the expansion ratio at a decompression point, and it tended to get larger with increase of the second pressure. These results show that the GAS method is very useful for the control of crystal size over a wide range.