Pressure–temperature state diagram for the phase relationships between benfluorex hydrochloride forms I and II: A case of enantiotropic behavior

Authors

  • Maria Barrio,

    1. Grup de Caracterització de Materials, Departament de Física i Enginyeria Nuclear, ETSEIB, Barcelona 08028, Catalonia, Spain
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  • Elisabetta Maccaroni,

    1. Department of Chemistry, Materials and Chemical Engineering “G. Natta”, Politecnico di Milano, I-20131 Milano, Italy
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  • Ivo B. Rietveld,

    Corresponding author
    1. Laboratoire de Chimie Physique (EA4066), Faculté de Pharmacie, Université Paris Descartes, 75006 Paris, France
    • Laboratoire de Chimie Physique (EA4066), Faculté de Pharmacie, Université Paris Descartes, 75006 Paris, France. Telephone: +33-1-53739675; Fax: + 33-1-43290592
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  • Luciana Malpezzi,

    1. Department of Chemistry, Materials and Chemical Engineering “G. Natta”, Politecnico di Milano, I-20131 Milano, Italy
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  • Norberto Masciocchi,

    1. Dipartimento di Scienze Chimiche e Ambientali, Università dell’Insubria, I-22100 Como, Italy
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  • René Céolin,

    1. Grup de Caracterització de Materials, Departament de Física i Enginyeria Nuclear, ETSEIB, Barcelona 08028, Catalonia, Spain
    2. Laboratoire de Chimie Physique (EA4066), Faculté de Pharmacie, Université Paris Descartes, 75006 Paris, France
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  • Josep-lluis Tamarit

    1. Grup de Caracterització de Materials, Departament de Física i Enginyeria Nuclear, ETSEIB, Barcelona 08028, Catalonia, Spain
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Abstract

The active pharmaceutical ingredient racemic benfluorex hydrochloride (benfluorex–HCl) has an interesting phase behavior due to an elusive solid–solid phase transition. The stability hierarchy between different phases is often determined based on heat-related experiments only or slurry interconversion. It is shown that if pressure and volume are taken into account, not only the phase equilibria are correctly positioned in the pressure–temperature phase diagram, but the experimental data also improves. Thus, it has been found that the racemic benfluorex–HCl is enantiotropic under “ordinary conditions” with polymorph II and polymorph I, respectively, being the low- and the high-temperature phases. Above ∼151 MPa, the system becomes monotropic and polymorph II is the single stable phase. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1073–1078, 2012

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