Water-mediated phase transformations of posaconazole. An intricate jungle of crystal forms
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04/2024
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01A - Journal article
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European Journal of Pharmaceutical Sciences
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195
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106722
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Elsevier
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Abstract
Posaconazole is a broad-spectrum antifungal agent exhibiting rich polymorphism. Up to now, a total of fourteen different crystal forms have been reported, sometimes with an ambiguous nomenclature, but less is known about their properties and stability relationships. Investigating the solid-state of a drug compound is essential to identify the most stable form under working conditions and to prevent the risk of undesired solid-phase transformations under processing and storage.
In this paper, we study posaconazole polymorphism by providing a description of its polymorphs, hydrates, and solvates. Powder X-ray diffraction (PXRD), dynamic vapor sorption (DVS), spectroscopic and thermal techniques were employed to characterize the different forms.
In addition, the solid-phase transformations of posaconazole in aqueous suspensions were studied by means of Raman microscopy. Surprisingly, we found that Form S, the crystal form contained in the marketed oral suspension, is not the most stable form in water. Form S readily converts to a more stable hydrate, i.e. Form A, after storage in water for two weeks. In the commercial oral formulation the conversion between the two forms is prevented by the presence of polysorbate 80. Such insights into the stabilizing excipient effects beyond particle dispersion are critical to formulators.
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0928-0987
1879-0720
1879-0720
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
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Peer review of the complete publication
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Gold
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Citation
Guidetti, M., Hilfiker, R., Kuentz, M., Bauer-Brandl, A., & Blatter, F. (2024). Water-mediated phase transformations of posaconazole. An intricate jungle of crystal forms. European Journal of Pharmaceutical Sciences, 195, 106722. https://doi.org/10.1016/j.ejps.2024.106722