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Bisoprolol and Bisoprolol-Valsartan Compatibility Studied by Differential Scanning Calorimetry, Nuclear Magnetic Resonance and X-Ray Powder Diffractometry

Skotnicki, Marcin; Aguilar, Juan A.; Pyda, Marek; Hodgkinson, Paul

Bisoprolol and Bisoprolol-Valsartan Compatibility Studied by Differential Scanning Calorimetry, Nuclear Magnetic Resonance and X-Ray Powder Diffractometry Thumbnail


Authors

Marcin Skotnicki

Juan A. Aguilar

Marek Pyda



Contributors

Abstract

Purpose The objective of this study was to evaluate the thermal behavior of crystalline and amorphous bisoprolol fumarate and its compatibility with amorphous valsartan. This pharmacologically relevant drug combination is a potential candidate for fixed-dose combination formulation. Methods DSC and TMDSC were used to examine thermal behavior of bisoprolol fumarate. SSNMR and XRPD were applied to probe the solid state forms. The thermal behavior of physical mixtures with different concentrations of bisoprolol and valsartan were examined by DSC and TMDSC, and the observed interactions were investigated by XRPD, solution- and solid-state NMR. Results The phase transitions from thermal methods and solid-state NMR spectra of crystalline and amorphous bisoprolol fumarate are reported. Strong interactions between bisoprolol fumarate and valsartan were observed above 60 C, resulting in the formation of a new amorphous material. Solution- and solid-state NMR provided insight into the molecular nature of the incompatibility. Conclusions A combined analysis of thermal methods, solution- and solid-state NMR and XRPD experiments allowed the investigation of the conformational and dynamic properties of bisoprolol fumarate. Since bisoprolol fumarate and valsartan react to form a new amorphous product, formulation of a fixed-dose combination would require separate reservoirs for bisoprolol and valsartan to prevent interactions. Similar problems might be expected with other excipients or APIs containing carboxylic groups.

Citation

Skotnicki, M., Aguilar, J. A., Pyda, M., & Hodgkinson, P. (2015). Bisoprolol and Bisoprolol-Valsartan Compatibility Studied by Differential Scanning Calorimetry, Nuclear Magnetic Resonance and X-Ray Powder Diffractometry. Pharmaceutical Research, 32(2), 414-429. https://doi.org/10.1007/s11095-014-1471-7

Journal Article Type Article
Acceptance Date Jul 24, 2014
Online Publication Date Aug 13, 2014
Publication Date Feb 1, 2015
Deposit Date May 13, 2015
Publicly Available Date Mar 28, 2024
Journal Pharmaceutical Research
Print ISSN 0724-8741
Electronic ISSN 1573-904X
Publisher Springer
Peer Reviewed Peer Reviewed
Volume 32
Issue 2
Pages 414-429
DOI https://doi.org/10.1007/s11095-014-1471-7
Keywords Bisoprolol, Compatibility, DSC, SSNMR, Valsartan.

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
© The Author(s) 2014. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.





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