Polymer-Induced Selective Nucleation of Mono or Ortho Polymorphs of Paracetamol through Swift Cooling of Boiled Aqueous Solution

A novel method of inducing the preferred polymorph of paracetamol through swift cooling of boiled aqueous solution in the presence of selective polymers has been identified. Depending upon the molecular interaction between the selected polymers such as nylon 6/6, polypropylene, and polyvinylchloride and the paracetamol, nucleation of either mono or ortho or both polymorphic forms of paracetamol were induced at well-distinguished supersaturation regions, whereas in the absence of the polymers, pure aqueous solution yielded only stable mono form. Nucleations induced by three different polymers have different induction periods. The percentage of mono, ortho, and mixed polymorphs nucleated at different supersaturation regions was estimated. Their external morphologies were identified through optical in situ microscopy, and their internal crystallographic structure was confirmed by powder X-ray diffraction (PXRD). It is found that the specific polymer-solute interaction induces nucleations with preferential growth of crystal facets having specific crystallographic orientations which is evident from the PXRD patterns of the grown crystals in which the prominent reflections observed corresponded to the crystal planes with which the nucleation began. Differential scanning calorimetry analysis revealed that the grown metastable ortho polymorph undergoes phase transformation at 89.35 degrees C, whereas the mono form does not show any phase transformation throughout the experimental temperature range of 40-190 degrees C.