Paracetamol Form II: An Elusive Polymorph through Facile Multicomponent Crystallization Routes

A simple route to crystallization of the pharmaceutically important paracetamol form II is reported. The method is based around multicomponent crystallization techniques, involving various second components containing carboxylic acid groups and a range of solvents. These crystallization experiments do not produce multicomponent molecular complexes, but instead they provide the conditions in which the metastable paracetamol form II is reliably produced in 100% yields and with stability of greater than one year. To date, batches of paracetamol form II have been produced easily on the 100 mg scale with clear potential for bulk production.