Batch and Tubular-Batch Crystallization of Paracetamol: Crystal Size Distribution and Polymorph Formation

Abstract

The crystallization of paracetamol from ethanol and methanol solutions was used to examine the possibility of using rapid cooling in a tubular flow-through apparatus to manipulate crystal size distribution and morphology. Flow through the tubular portion of the apparatus was laminar, and hence, the device, including a receiving vessel, is referred to as a laminar-flow tubular crystallizer (LFTC). Undersaturated solution entered the tubular portion of the LFTC and was rapidly cooled to temperatures far below solubility conditions. Experimental results were also obtained using a typical batch configuration with the same solute and solvents, but with significantly lower cooling rates than in the LFTC. The crystals produced in the flow-through apparatus were of smaller mean size than those obtained from batch crystallizations, and evidence was found that using the rapid-cooling technique could lead to the generation of kinetically stable polymorphs. Moreover, the total run time required to relieve all of the generated supersaturation (i.e., produce a fixed mass of crystals) was significantly less with the flow-through device than with the batch unit.