Effects of operating conditions on agglomeration and habit of paracetamol crystals in anti-solvent crystallization

Abstract

Effects of agitation speed and feeding rate on agglomeration and habit of paracetamol crystals in anti-solvent crystallization from water–acetone mixture are reported. Water is used as anti-solvent and is added in a semi-batch manner to a baffled 1-l crystallizer equipped with a marine-type impeller. A simple new method to characterize agglomeration degree has been proposed. Results show that agglomeration degree of crystals depends on particle size and elevated agitation reduces agglomeration degree of big particles. Particle mean size exhibits a maximum with increasing agitation intensity in the range of 200–600 rpm, which is explained from the perspective of anti-solvent dispersion and crystal agglomeration/disruption. Agglomeration degree of products deteriorates with increasing feeding rate ranging from 1 to 20 g/min due to enhanced nucleation. Crystal habit changes when feeding rate is altered, mainly in the faces of [0 0 1] and [1 1 0]. Focused beam reflectance measurement (FBRM) was used to monitor indirectly the particle size distribution in situ. The data demonstrated that FBRM may potentially be used as a tool to control crystallization process.