ABSTRACT
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-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 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-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.
Subject(s)
Cladribine/chemistry , Immunosuppressive Agents/chemistry , beta-Cyclodextrins/chemistry , 2-Hydroxypropyl-beta-cyclodextrin , Administration, Oral , Calorimetry, Differential Scanning , Cladribine/administration & dosage , Humans , Immunosuppressive Agents/administration & dosage , Multiple Sclerosis/drug therapy , Spectrum Analysis/methodsABSTRACT
Curosurf is a pulmonary surfactant used in the treatment or prophylaxis of neonatal respiratory distress syndrome. It contains low molecular weight hydrophobic apoproteins and a series of lipids including phosphatidylcholines, lisophosphatidylcholines, phosphatidylethanolamines, sphingomyelins, phosphatidylinositols, phosphatidylglycerols and phosphatidylserines. In the present work, a rapid method to qualitatively map the Curosurf phospholipid classes without prior derivatization or chromatographic separations is described. In particular, a series of specific electrospray tandem mass spectrometric (ES-MS/MS) experiments, i.e. product ion, precursor ion and neutral loss scans, were chosen on the basis of the chemical nature of each phospholipid class and then used to identify single components of the commercial suspension, directly infused into the ion source of the mass spectrometer.