Challenging identification of polymorphic mixture: Polymorphs I, II and III in olanzapine raw materials

• Published in: International journal of pharmaceutics Vol. 556; pp. 125 - 135
• Main Authors: Testa, Carla G., Prado, Livia D., Costa, Rogéria N., Costa, Michelle L., Linck, Yamila G., Monti, Gustavo A., Cuffini, Silvia L., Rocha, Helvécio V.A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.02.2019
• Subjects: Olanzapine; Polymorphism; Solid state nuclear magnetic resonance; Thermal analysis; X-ray diffraction; X-ray diffraction; Olanzapine; Solid state nuclear magnetic resonance; Thermal analysis; Polymorphism; olanzapine; polymorphism; solid state nuclear magnetic resonance; thermal analysis
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2018.12.008

[Display omitted] Olanzapine (OLZ), a drug for the treatment of schizophrenia, presents in more than 60 crystal forms. Polymorphs I, II and III were reported, however, the preparation conditions for pure II and III have not been reported. Polymorph IV was reported but this form is actually polymorph II described at different temperature. The diversity of solid forms of OLZ, the change in the nomenclature found in the literature and the presence of polymorphic mixture in samples, increase the difficulty for a correct solid state characterization. Therefore, the goal was the polymorphic identification of three OLZ raw materials, highlighting the limitation of conventional techniques (typically used in analytical control) and the necessity to use a combination of advanced ones to solve this challenge. The samples were studied by conventional techniques such as powder X-ray diffraction, thermoanalytical techniques, infrared spectroscopy. In apart from that, synchrotron powder X-ray diffraction (SPXRD) and solid state nuclear magnetic resonance (ss-NMR) were used. All samples were in accordance with the pharmacopoeia criteria. However, the conventional techniques were not specific for the complete polymorphic identification. Therefore, a combination of advanced techniques (SPXRD and ss-NMR) was necessary to identify the mixture of polymorphs (I, II and III) in all samples.