Low molecular weight poly(ethylene glycol) as an environmentally benign solvent for pharmaceutical crystallization and precipitation

Low molecular weight poly(ethylene glycol) (PEG300) is examined as a possible environmentally benign replacement solvent for volatile organic solvents commonly used in crystallization and precipitation operations in pharmaceutical processing. It is shown to have solvating power comparable in magnitude to that of 2-propanol or methanol for model compounds including ibuprofen, salicylic acid, and amino acids. UNIFAC can be used to predict solvent effects for uncharged solutes. Antisolvent precipitation of salicylic acid from either aqueous PEG300 or methanol by water addition indicated a longer induction time for PEG solutions primarily due to a larger crystal-solution interfacial energy. Induction time measurements of glutamic acid precipitation with PEG or 2-propanol again indicated a higher interfacial energy for the PEG solution. Crystal growth rates of salicylic acid and glutamic acid were somewhat lower in PEG solutions than in aliphatic alcohols owing to an interfacial effect and not to transport limitations in these higher viscosity solutions. Crystal habit and structure were found to be the same in PEG and alcohol solutions.