Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 97, Issue 9, Pages 3897-3906Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.21283
Keywords
cladribine; cyclodextrins; inclusion compounds; FT-IR; NMR spectroscopy; thermal analysis; oral drug delivery
Funding
- Merck Serono International S.A., Geneva, Switzerland
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available