Djordjević Filijović, Nataša, Antonijević, Milan D. ORCID: 0000-0002-5847-7886 , Pavlović, Aleksandar, Vučković, Ivan, Nikolić, Katarina and Agbaba, Danica (2015) The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations. Drug Development and Industrial Pharmacy, 41 (3). pp. 502-514. ISSN 0363-9045 (Print), 1520-5762 (Online) (doi:https://doi.org/10.3109/03639045.2014.884114)

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Abstract

Stress stability testing represents an important part of the drug development process. It is used as an important tool for the identification of degradation products and degradation pathways, as well as for the assessment of changes in physical form of drug molecules. The impact of excipients on the stability of olanzapine confirms that levels of impurities and degradants are limiting parameters and are therefore used for stability evaluation. The major degradation product of olanzapine was identified as 2-methyl-5,10-dihydro-4H-thieno[2,3-b][1,5]benzodiazepine-4-one (III). The structure of III was determined by using LC-MS, IR and NMR. Compatibility and stress stability results demonstrated that tablet formulations of olanzapine are sensitive to temperature and moisture. In samples protected from moisture, the increase in concentration of III was shown to be highly temperature dependent and the degradation followed zero-order kinetics. In addition, studies of olanzapine with excipients and in formulated tablets revealed polymorphic phase changes in some samples, influenced by a combination of stress temperature and humidity conditions. Polymorphic transitions were monitored using x-ray powder diffraction (XRPD) analysis and exhibited no correlation between the phase change (appearance of a new polymorph) and the degradation process.

Item Type:	Article
Uncontrolled Keywords:	drug–excipient interactions, impurities, olanzapine, polymorphism, stress testing
Subjects:	R Medicine > RS Pharmacy and materia medica
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Related URLs:	Publisher
Last Modified:	02 May 2020 12:24
URI:	http://gala.gre.ac.uk/id/eprint/11370

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