Effects of harvesting and cooling on crystallization and transformation of orthorhombic paracetamol in ethanolic solution

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

“…Anyway, the high transformation rate supports our view that a solvent-induced transformation is the main reason why solution-grown form II crystals are contaminated with small amounts of form I. The possibility of primary nucleation of both forms in solution and prevalence of form II due to a higher nucleation rate cannot be ruled out, however it seems highly unlikely based on previously published data (19) and considering that in a seeded solution, primary nucleation is not expected to take place. In other words, we infer from our studies that the stable form I does not arise directly by a primary nucleation process in the highly supersaturated solution but is the product of a solvent mediated transformation process of the metastable orthorhombic form II.…”

“…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.…”

Total Phenol, Flavanoid and Antioxidant Activity of Physalis angulata Leaves Extract by Subcritical Water Extraction

“…Because of some physical or chemical barriers, it can not be removed completely from the product by separation such as drying or evaporation. Eventhough some organic solvents are allowed of daily exposures of around 50 mg/day and less, the possibility of the residual solvents in acceptable limit may induce phase transformation and jeopardize the psicoxhemical stability of an active substance and finally the quality of the dossage form may exist, for instance the effect of methylene chloride on the crystallinity of ampicillin tryhydrate and the redsidual ethanol on phase transformation of orthorhombic paracetamol (Grodowska & Parczewski, 2010;Nojavan et al, 2005;Al-Zoubi et al, 2002). Therefore, pharmaceutical companies constantly attempt to eliminate the usage of organic solvents with those more environmentally friendly such as water, supercritical CO 2 , ionic liquids etc as a potential of reaction media.…”

Growth promotion by H2O in organic solvent—selective isolation of a target polymorph

“…The bulk APIs need to meet polymorphic purity specifications considering the potential differences in physical properties and bioavailability between different polymorphs of pharmaceutical solids [2]. The challenges posed by polymorphism of pharmaceutical solids to the successful design and scale-up of API crystallization processes have gained wide awareness [3][4][5][6][7][8]. Aside from the challenges to discover and characterize potential polymorphs of an API, it is often difficult to grow or isolate a target form with 100% polymorphic purity robustly and efficiently in large-scale processing [4,5,8].…”