FarFaR - Pharmacy Repository
University of Belgrade, Faculty of Pharmacy
    • English
    • Српски
    • Српски (Serbia)
  • English 
    • English
    • Serbian (Cyrillic)
    • Serbian (Latin)
  • Login
View Item 
  •   FarFaR
  • Pharmacy
  • Radovi istraživača / Researchers’ publications
  • View Item
  •   FarFaR
  • Pharmacy
  • Radovi istraživača / Researchers’ publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations

Authorized Users Only
2015
Authors
Đorđević-Filijović, Nataša
Antonijević, Milan D.
Pavlović, Aleksandar
Vucković, Ivan M.
Nikolić, Katarina
Agbaba, Danica
Article (Published version)
Metadata
Show full item record
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 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 testing
Source:
Drug Development and Industrial Pharmacy, 2015, 41, 3, 502-514
Publisher:
  • Informa Healthcare, London
Funding / projects:
  • Synthesis, Quantitative Structure and Activity Relationship, Physico-Chemical Characterisation and Analysis of Pharmacologically Active Substances (RS-172033)

DOI: 10.3109/03639045.2014.884114

ISSN: 0363-9045

PubMed: 24611817

WoS: 000351499000020

Scopus: 2-s2.0-84925014592
[ Google Scholar ]
6
5
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/2415
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - 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 . .

DSpace software copyright © 2002-2015  DuraSpace
About FarFaR - Pharmacy Repository | Send Feedback

OpenAIRERCUB
 

 

All of DSpaceCommunitiesAuthorsTitlesSubjectsThis institutionAuthorsTitlesSubjects

Statistics

View Usage Statistics

DSpace software copyright © 2002-2015  DuraSpace
About FarFaR - Pharmacy Repository | Send Feedback

OpenAIRERCUB