Polymorphism on leflunomide: stability and crystal structures

Two polymorphs of Leflunomide were found and studied (form I and II). Both of them were characterized by X-ray powder diffraction and thermal analysis. Single crystals were obtained and both structures were solved. Forms I and II crystallize in the space group P2(1)/c with two and one independent molecules per asymmetric unit, respectively. Thermodynamic stability of the two forms is assessed by differential scanning calorimetry. The cohesion in the crystal of form I (the more stable) is provided by both by H bonding as well as pi...pi interactions, while in form II it is given only by the former. The independent molecules in form I adopt different conformations thus allowing for a larger number of intermolecular interactions.     

Comparison of medium, temperature, and length of incubation for detection of vancomycin-resistant Enterococcus

Campylobacter (Campy; BD Diagnostics, Sparks, MD), Spectra VRE (Remel, Lenexa, KS), and bile-esculin-azide-vancomycin (BEAV; Remel) agars were compared for their ability to detect vancomycin-resistant enterococci (VRE) in 750 stool specimens. The media were compared at 24 h and 48 h of incubation at 35°C and 42°C. When incubated for 24 h at 35°C, Campy was the most sensitive (97.8%) and specific (99.9%) but was comparable to Spectra, which has a sensitivity of 95.6% and a specificity of 99.1%, whereas BEAV was significantly less sensitive (90%) and specific (96.1%). Incubation at 42°C or extended incubation at 35°C for 48 h yielded no advantage over incubation at 35°C for 24 h.     

Comparison of two commercially available selective media to screen for vancomycin-resistant enterococci.

Campylobacter medium (CAMPY, Becton Dickinson [BD] Microbiology Systems, Cockeysville, MD) and Vancomycin Screen Agar (VSA, BD) were compared for their ability to screen for vancomycin-resistant Enterococcus (VRE) from primary plates. A microdilution minimal inhibitory concentration (MIC) assay (Pasco, BD) served as the reference vancomycin MIC. In the random sample of 200 enterococcal clinical isolates tested, the distribution of isolates was as follows: Enterococcus faecium, 113 (97 VRE); Enterococcus faecalis, 71(12 VRE); Enterococcus gallinarum, 10; and Enterococcus casseliflavus, 6. Of the 75 vancomycin-susceptible strains, none grew on CAMPY and 4 grew on VSA, whereas all 109 VRE isolates grew on both screen plates. Of the 16 strains with a Van C phenotype, ie, E. gallinarum and E. casseliflavus, 2 grew on CAMPY and 14 on VSA. Of the 899 clinical specimens plated onto both agars, 45 of 67 VRE were detected with both media, 20 were detected only with CAMPY and 2 were not detected by either screen plate. CAMPY compared with VSA as a primary plating medium was more sensitive and, when used to screen for VRE isolates from primary plates, was more specific for strains displaying Van A and B phenotypes.     

Intra and Inter-Molecular Interactions Dictate the Aggregation State of Irinotecan Co-Encapsulated with Floxuridine Inside Liposomes

PURPOSE: The inter/intramolecular interactions between drugs (floxuridine, irinotecan) and excipients (copper gluconate, triethanolamine) in the dual-drug liposomal formulation CPX-1 were elucidated in order to identify the physicochemical properties that allow coordinated release of irinotecan and floxuridine and maintenance of the two agents at a fixed, synergistic 1:1 molar ratio. METHODS: Release of irinotecan and floxuridine from the liposomes was assessed using an in vitro-release assay. Fluorescence, Nuclear Magnetic Resonance spectroscopy (NMR) and UV-Vis were used to characterize the aggregation state of the drugs within the liposomes. RESULTS: Coordinated release of the drugs from liposomes was disrupted by removing copper gluconate. Approximately 45% of the total irinotecan was detectable in the copper-containing CPX-1 formulation by NMR, which decreased to 19% without copper present in the liposomal interior. Formation of higher order, NMR-silent aggregates was associated with slower and uncoordinated irinotecan release relative to floxuridine and loss of the synergistic drug/drug ratio. Solution spectroscopy and calorimetry revealed that while all formulation components were required to achieve the highest solubility of irinotecan, direct drug-excipient binding interactions were absent. CONCLUSIONS: Long-range interactions between irinotecan, floxuridine and excipients modulate the aggregation state of irinotecan, allowing for simultaneous release of both drugs from the liposomes.