The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations
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2015
Authors
Đorđević-Filijović, NatašaAntonijević, Milan D.

Pavlović, Aleksandar
Vucković, Ivan M.
Nikolić, Katarina

Agbaba, Danica

Article (Published version)

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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 excipien...ts 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.
Keywords:
Drug-excipient interactions / impurities / olanzapine / polymorphism / stress testingSource:
Drug Development and Industrial Pharmacy, 2015, 41, 3, 502-514Publisher:
- Informa Healthcare, London
Funding / projects:
DOI: 10.3109/03639045.2014.884114
ISSN: 0363-9045
PubMed: 24611817
WoS: 000351499000020
Scopus: 2-s2.0-84925014592
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PharmacyTY - JOUR AU - Đorđević-Filijović, Nataša AU - Antonijević, Milan D. AU - Pavlović, Aleksandar AU - Vucković, Ivan M. AU - Nikolić, Katarina AU - Agbaba, Danica PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2415 AB - 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. PB - Informa Healthcare, London T2 - Drug Development and Industrial Pharmacy T1 - The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations VL - 41 IS - 3 SP - 502 EP - 514 DO - 10.3109/03639045.2014.884114 ER -
@article{ author = "Đorđević-Filijović, Nataša and Antonijević, Milan D. and Pavlović, Aleksandar and Vucković, Ivan M. and Nikolić, Katarina and Agbaba, Danica", year = "2015", 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.", publisher = "Informa Healthcare, London", journal = "Drug Development and Industrial Pharmacy", title = "The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations", volume = "41", number = "3", pages = "502-514", doi = "10.3109/03639045.2014.884114" }
Đorđević-Filijović, N., Antonijević, M. D., Pavlović, A., Vucković, I. M., Nikolić, K.,& Agbaba, D.. (2015). The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations. in Drug Development and Industrial Pharmacy Informa Healthcare, London., 41(3), 502-514. https://doi.org/10.3109/03639045.2014.884114
Đorđević-Filijović N, Antonijević MD, Pavlović A, Vucković IM, Nikolić K, Agbaba D. The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations. in Drug Development and Industrial Pharmacy. 2015;41(3):502-514. doi:10.3109/03639045.2014.884114 .
Đorđević-Filijović, Nataša, Antonijević, Milan D., Pavlović, Aleksandar, Vucković, Ivan M., Nikolić, Katarina, Agbaba, Danica, "The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations" in Drug Development and Industrial Pharmacy, 41, no. 3 (2015):502-514, https://doi.org/10.3109/03639045.2014.884114 . .