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

• Published in: Journal of pharmaceutical sciences Vol. 97; no. 9; pp. 3897 - 3906
• Main Authors: Van Axel Castelli, Valeria, Trivieri, Giovanni, Zucchelli, Ilaria, Brambilla, Luigi, Barbuzzi, Tony, Castiglioni, Chiara, Paci, Maurizio, Zerbi, Giuseppe, Zanol, Margherita
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2008; Wiley; American Pharmaceutical Association
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; beta-Cyclodextrins - chemistry; Biological and medical sciences; Calorimetry, Differential Scanning; cladribine; Cladribine - administration & dosage; Cladribine - chemistry; cyclodextrins; FT-IR; General pharmacology; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - chemistry; inclusion compounds; Medical sciences; Multiple Sclerosis - drug therapy; NMR spectroscopy; oral drug delivery; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Spectrum Analysis - methods; thermal analysis; Antineoplastic agent; Drug; Purine nucleoside; Fourier transformation; Pharmaceutical technology; Oral administration; FT-IR; NMR spectrometry; Deoxyribonucleoside; cyclodextrins; Infrared spectrometry; Cyclodextrin; Antimetabolic; oral drug delivery; Cladribine; inclusion compounds; Thermal analysis; Inclusion compound; NMR spectroscopy
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.21283

Parenterally administered cladribine (2‐chloro‐2′‐deoxyadenosine) 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‐hydroxypropyl‐β‐cyclodextrin (2‐HP‐β‐CD). Several techniques were used to analyse the complex both in solution and in the solid state. These analyses provided evidence that the inclusion 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‐β‐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. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3897–3906, 2008