Preferential Orientation Effect of Polymers on Paracetamol Crystallization: Experiments and Modeling

Crystallization is one of the most important unit operations in the quality control of pharmaceutical products. For this study, a polymer-induced heteronucleation method was selected to investigate the effect of nylon 66 (PA66), polyester (PET), and polypropylene (PP) films on the crystal growth of paracetamol by coupling experiments with modeling. The result of induction time indicated that the order of induced effect was PA66 > PET > PP > no template. X-ray photoelectron spectroscopy results indicated the different functional groups on the surface of films. The crystal habits and powder X-ray diffraction results indicated that preferential orientation along certain facets occurred for PA66 and PET, and the results of in situ Raman microscopy verified the different concentration trends near different films, which is consistent with the preferential orientation effect of films. The results of molecular simulation indicated that the difference in van der Waals and electrostatic interaction, as well as H-bond donor/acceptor on the polymer films, is the origin of the preferential orientation effect for paracetamol crystallization. The PP film modified with similar functional groups of PA66 on surfaces caused the same preferential orientation effect as PA66, which verified the functional-induced mechanism of the preferential orientation. This study could contribute to the investigation of the mechanism of polymer-induced heteronucleation and screen out the efficient templates.