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Communication Dans Un Congrès Année : 2023

Hydration-dehydration mechanism of prednisolone sesquihydrate investigated by thermal analysis

Mécanismes d’Hydratation/Déshydratation du sesquihydrate de Prednisolone: étude par analyse thermique

Résumé

The pharmaceutical development of an active molecule designed for an oral dosage requires the knowledge of its different solid states, which can be amorphous, anhydrous crystalline or solvated crystalline [1]. For crystalline forms, whether solvated or not, the relative stability must be established to choose the most suitable form for developing a drug and to guarantee its chemical and physical stability, while taking into account the solubility, the rate of dissolution and bioavailability. Prednisolone is a worldwide used corticosteroid to treat types of allergies, inflammatory conditions, autoimmune disorders, and cancers. It recently regains interest for treating covid-19 diseases. This molecule exhibits a solid-state landscape with several crystalline phases; to date: two polymorphs (Form I and II), and a sesquihydrate (1.5 H2O).Thermal behavior of the sesquihydrate was studied by several authors [2] [3], which concluded on a classical pathway for organic hydrates: full thermal dehydration led directly to anhydrous Form 1, prior to the latter melting/degradation at circa 220°C. However, during our attempts to thoroughly study this dehydration process, such behavior was never encountered, and the dehydration mechanism appeared much more complicated than that previously reported. In this work, we present the thermal behavior of prednisolone sesquihydrate based on TGA, DSC, TR-XRD, TR-microscopy and DVS analyses. These investigations reveal the existence of third anhydrous form (previously unknown) which was confirmed to be a isomorphous dehydrate [4] [5]. Then, a classification of the sesquihydrate from an energetic and mechanistic points of view is proposed.Références[1] Healy, A.M.; Worku, Z.A.; Kumar, D.; Madi, A.M. Adv. Drug Deliv. Rev. (2017) 117, 25-46[2] Veiga, M.D.; Cadorniga, R.; Lozano, R. Thermochim. Acta (1985) 96, 111-115 [3] Suitchmezian, V.; Jess, I.; Sehnert, J.; Seyfarth, L.; Senker, J.; Näther, C. Cryst. Growth Des. (2008) 8, 98-107[4] Stephenson, G.A.; Groleau, E.G.; Kleemann, R.L.; Xu, W.; Rigsbee, D.R. J. Pharm. Sci. (1998) 87, 536–542[5] Fours, B.; Cartigny, Y.; Petit, S.; Coquerel, G. Faraday Discuss. (2015) 179, 475–488.
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Dates et versions

hal-04105460 , version 1 (24-05-2023)

Identifiants

  • HAL Id : hal-04105460 , version 1

Citer

Nicolas Couvrat, Aurélien Lemercier, Morgane Sanselme, Yohann Cartigny, Yohann Corvis, et al.. Hydration-dehydration mechanism of prednisolone sesquihydrate investigated by thermal analysis. Journées de Calorimétrie et d'Analyse Thermique 53, AgroParisTech, May 2023, Palaiseau, France. ⟨hal-04105460⟩
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