Parenterally administered cladribine (2-chloro-2'-alpha eoxyadenosine) has demonstrated promising efficacy and safety in clinical trials in patients with multiple sclerosis (MS). An oral formulation of this small molecule would be an attractive option for patients. Here, we describe the chemical characterisation of the inclusion complex between cladribine and the drug carrier molecule 2-hydroxyproryl-beta-cyclodextrin (2-HP-beta-CD). Several techniques were used to analyse the complex both in solution and in the solid state. These analyses provided evidence that the inclusicn complex cannot be simply reduced to the sum of the two species, as it shows behaviour different from that of the physical mixture of the two components. Furthermore, solution nuclear magnetic resonance spectroscopy demonstrated the existence of an inclusion complex between cladribine and 2-HP-beta-CD. Importantly, analysis of a tablet formulation demonstrated that the chemical characteristics of the inclusion complex are not affected by the manufacturing process, and that the complex is stable during storage. This tablet formulation is currently under investigation for the treatment of patients with MS. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3897-3906, 2008.

Van Axel Castelli, V., Trivieri, G., Zucchelli, I., Brambilla, L., Barbuzzi, T., Castiglioni, C., et al. (2008). Characterisation of an inclusion complex between cladribine and 2-hydroxypropyl-beta-cyclodextrin. JOURNAL OF PHARMACEUTICAL SCIENCES, 97(9), 3897-3906 [10.1002/jps.21283].

Characterisation of an inclusion complex between cladribine and 2-hydroxypropyl-beta-cyclodextrin

PACI, MAURIZIO;
2008

Abstract

Parenterally administered cladribine (2-chloro-2'-alpha eoxyadenosine) has demonstrated promising efficacy and safety in clinical trials in patients with multiple sclerosis (MS). An oral formulation of this small molecule would be an attractive option for patients. Here, we describe the chemical characterisation of the inclusion complex between cladribine and the drug carrier molecule 2-hydroxyproryl-beta-cyclodextrin (2-HP-beta-CD). Several techniques were used to analyse the complex both in solution and in the solid state. These analyses provided evidence that the inclusicn complex cannot be simply reduced to the sum of the two species, as it shows behaviour different from that of the physical mixture of the two components. Furthermore, solution nuclear magnetic resonance spectroscopy demonstrated the existence of an inclusion complex between cladribine and 2-HP-beta-CD. Importantly, analysis of a tablet formulation demonstrated that the chemical characteristics of the inclusion complex are not affected by the manufacturing process, and that the complex is stable during storage. This tablet formulation is currently under investigation for the treatment of patients with MS. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3897-3906, 2008.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10
English
Con Impact Factor ISI
Cladribine; Cyclodextrins; FT-IR; Inclusion compounds; NMR spectroscopy; Oral drug delivery; Thermal analysis
Van Axel Castelli, V., Trivieri, G., Zucchelli, I., Brambilla, L., Barbuzzi, T., Castiglioni, C., et al. (2008). Characterisation of an inclusion complex between cladribine and 2-hydroxypropyl-beta-cyclodextrin. JOURNAL OF PHARMACEUTICAL SCIENCES, 97(9), 3897-3906 [10.1002/jps.21283].
Van Axel Castelli, V; Trivieri, G; Zucchelli, I; Brambilla, L; Barbuzzi, T; Castiglioni, C; Paci, M; Zerbi, G; Zanol, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/27155
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