Hydration, stability, and phase transformations of a new antitumor drug.
We studied hydration equilibria and phase transformations in a cytotoxic drug (BBR3576). The original sample is a hydrated compound that undergoes a structural phase transition when it looses about half of its structural water. Such a structural transition is completely reversible: the partially dehydrated form is stable up to 130 degrees C (or up to 140 degrees C for several minutes) and reverts to the original form upon rehydration. Completely different phase relationships are observed if an original sample is fully dehydrated: when all water has been released, a metastable anhydrous phase forms, which undergoes an irreversible exothermic conversion to a stable phase. Upon rehydration at room temperature of such an anhydrous phase, a new hydrated form is obtained, which is definitely different from the original one.
C.S.G.I., Dipartimento di Chimica Fisica dell'Università degli Studi di Pavia, Via Taramelli 16, 27100 Pavia, Italy. marini@matsci.unipv.it
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Marini
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Berbenni
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Bruni
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Cofrancesco
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Margheritis
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Orlandi
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Villa
D000970:Antineoplastic Agents / Q000032:analysis* / Q000737:chemistry* / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning / Q000379:methods; D004355:Drug Stability; D006576:Heterocyclic Compounds, 4 or More Rings / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D013818:Thermogravimetry / Q000379:methods; D014867:Water / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D014961:X-Ray Diffraction / Q000379:methods
D000970:Antineoplastic Agents; C492575:BBR 3576; D006576:Heterocyclic Compounds, 4 or More Rings; D011720:Pyrazoles; D014867:Water