Effect of operating conditions on batch and continuous paracetamol crystallization in an oscillatory flow mesoreactor

Abstract

The batch and continuous crystallization of paracetamol from aqueous solutions is studied in a novel oscillatory flow mesoreactor equipped with smooth periodic constrictions. The aim of this study is to evaluate the influence of the operating and thermodynamic variables on the size of the crystals for enhanced direct crystallization of micronized powders. It was found that mixing intensity, supersaturation and temperature determine the crystal size properties. Evaluating the results according to the classical nucleation theory, it was observed that the kinetic and the thermodynamic parameters are mainly influenced by the mixing intensity and by the crystallization temperature, respectively. The continuous-flow operation mode was revealed to be more suitable in the production of inhalable size particles because it provides smaller residence times and reduced friction, breakage and aggregation phenomena. Growth kinetic data were also obtained. This new reactor showed great potential to be used for direct crystallization of this drug for pulmonary drug delivery.

Designs of continuous-flow pharmaceutical crystallizers: developments and practice

“…Oscillatory baffled crystallizers (OBCs, or "oscillatory/pulsed flow crystallizers", Fig. 3a and b) have been used for cooling crystallization, 18,40,70,71 co-crystallization, 43 and anti-solvent crystallization. 72 OBCs enhance mixing while having low average forward flow rates by inserting periodically spaced baffles that cause turbulent eddies upon interaction with the oscillatory flow in the pipe.…”

Solid-liquid axial dispersion performance of a mesoscale continuous oscillatory flow crystalliser with smooth periodic constrictions using a non-invasive dual backlit imaging technique

“…SPC mesoscale OFR, where oscillatory flow mixing promoted nucleation at quiescent conditions. Cruz et al [9] studied the batch and continuous crystallisation of paracetamol in a 4 mm i.d. SPC mesoscale OFR, demonstrating the effect of oscillatory mixing conditions on paracetamol crystal size and size distribution.…”

The effect of particle aspect ratio on spatially and angularly resolved vis-NIR spectroscopy of suspensions

“…Today, there is a growing number of processes which require techniques for real-time characterisation of particle shape changes. 1 The particle morphology (e.g., size, shape) and concentration of a suspension often critically dictate the performance of a formulation in many areas, such as in the chemical or pharmaceutical industry, and therefore need to be closely controlled. So far, most analytical approaches describe the particles with different geometries using the equivalent spherical diameter of the particle.…”