Pimozide and Adipic Acid: A New Multicomponent Crystalline Entity for Improved Pharmaceutical Behavior
Alessandra Buscarini,
Michael J. Zaworotko,
Catiúcia R. M. O. Matos,
Fabrizia Grepioni,
Laura Contini,
Doretta Capsoni,
Valeria Friuli,
Lauretta Maggi,
Giovanna Bruni
Affiliations
Alessandra Buscarini
Department of Chemistry, Physical Chemistry Section & C.S.G.I. (Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase), University of Pavia, Via Taramelli 16, 27100 Pavia, Italy
Michael J. Zaworotko
Department of Chemical Sciences and Bernal Institute, University of Limerick, V94 T9PX Limerick, Ireland
Catiúcia R. M. O. Matos
Department of Chemical Sciences and Bernal Institute, University of Limerick, V94 T9PX Limerick, Ireland
Fabrizia Grepioni
Dipartimento di Chimica “Giacomo Ciamician”, Università di Bologna, Via Selmi 2, 40126 Bologna, Italy
Laura Contini
Dipartimento di Chimica “Giacomo Ciamician”, Università di Bologna, Via Selmi 2, 40126 Bologna, Italy
Doretta Capsoni
Department of Chemistry, Physical Chemistry Section & C.S.G.I. (Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase), University of Pavia, Via Taramelli 16, 27100 Pavia, Italy
Valeria Friuli
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Lauretta Maggi
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Giovanna Bruni
Department of Chemistry, Physical Chemistry Section & C.S.G.I. (Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase), University of Pavia, Via Taramelli 16, 27100 Pavia, Italy
Pimozide is a first-generation antipsychotic used in the treatment of schizophrenia, Gilles de la Tourette syndrome, and other chronic psychoses. Its in vivo efficacy is limited by poor solubility and consequent poor bioavailability. Therefore, adipic acid was used as a coformer for the preparation of a binary product with improved pharmaceutical properties. The thermal behavior of the liquid-assisted grinding products of compositions included in the range 0.1 XPMZ [PMZH]2[adipate]. The crystalline product was characterized, from a pharmaceutical perspective, in terms of solubility and wettability (contact angle). Then, a tablet formulation was developed, and its dissolution behavior was compared to a commercial product considered as a reference. The new entity showed improved pharmaceutical properties in terms of solubility and wettability compared to the pure drug in both deionized water and bio-relevant fluids simulating oral administration in fed and fasted conditions. The tablets containing the new crystalline form can make this virtually insoluble drug available for absorption within minutes regardless of the variability in gastric conditions.
