Effects of initial concentration and seeding procedure on crystallisation of orthorhombic paracetamol from ethanolic solution

Overview of Secondary Nucleation: From Fundamentals to Application

“…The polymorphic seed is expected to be an excellent strategy to control the secondary nucleation and achieve the desired polymorphism outcome . There have been many reports about polymorphic seeding , and seeding procedures on the polymorphism outcome in previous literature. Modification of controlled crystal products can be effectively achieved during nucleation by adding the desired form of seed to override spontaneous nucleation .…”

Effects of Moisture and Residual Solvent on the Phase Stability of Orthorhombic Paracetamol

“…However, the only reproducible method is the seeding technique (14). This process has been extensively studied (18)(19)(20) and it was found that harvesting and drying procedures are the most critical steps affecting polymorphic purity (14), because prolonged contact with the solvent induces transformation to form I (19). Regarding the long-term polymorphic stability of the orthorhombic crystals, conflicting data can be found in the literature, depending on the crystallization method (melt or solution) or even on the solvent used.…”

“…Although the seeded crystallization method has been optimized (20), and the solvent-mediated transformation has been investigated (19), until today there has been no systematic study on the mechanism of the solid-state transformation to the monoclinic form during storage. Thus, the present study attempts to elucidate the factors affecting stability of orthorhombic paracetamol, and particularly the effects of atmospheric relative humidity (RH) and residual solvent on crystalline samples of different initial monoclinic content, by applying powder X-ray diffraction (PXRD) in combination with gravimetric dynamic moisture sorption, thermo-analytical methods, vibrational spectroscopy and optical microscopy.…”

Application of Selective Crystallization Methods To Isolate the Metastable Polymorphs of Paracetamol: A Review

“…This seeding technique was later applied by Al-Zoubi et al − in a larger scale crystallizer with 1 L of volume, and the influence of several conditions were evaluated. It was found that the yield generally increases with the agitation rate, the harvesting time, and the initial concentration and decreases with the cooling temperature (i.e., the temperature of the cooling bath and also the final temperature), whereas the content of form II in the final product increases with both the cooling temperature and the agitation rate.…”