Guy Van Den Mooter

The purpose of this study was to investigate the influence of the composition of in-vitro azoreducing systems on the degradation kinetics of the model compound amaranth. The degradation kinetics of amaranth were determined under anaerobic conditions both in rat caecal content (ex-vivo) and in a variety of in-vitro degradation media derived from rat caecal content. It was observed that the reducing activity was highly dependent on the preparation method and composition of the degradation medium. In pure rat caecal content, the degradation of amaranth was apparent first order (k = 0.044+0.002 min−1), while dilution of the rat caecal content resulted in an apparentzero-orderdegradation. Both apparentzero- and first-order degradations were also observed in media made up of diluted rat caecal content to which cofactors such as NADP, D-glucose-6-phosphate, glucose-6-phosphate dehydrogenase and Bz were added. This study demonstrates that in-vitro azo-reducing kinetics are dependent on the composition and mode of preparation of the in-vitro media used. This has to be taken into account when evaluating the degradability of azo-aromatic drug delivery systems in-vitro.

The purpose of this study was to elucidate the physical structure of solid dispersions of the antiviral agent UC-781 (N-[4-chloro-3-(3-methyl-2-butenyloxy)phenyl]-2-methyl-3-furancarbo-thioamide) with polyvinylpyrrolidone (PVP K30). Solid dispersions were prepared by co-evaporating UC-781 with PVP K30 from dichloromethane. The physicochemical properties of the dispersions were evaluated in comparison with the physical mixtures by differential scanning calorimetry (DSC), X-ray powder diffraction, and FT-IR spectroscopy. We investigated the single crystal structure of pure UC-781. The data from single crystal analysis showed that UC-781 crystallized with orthorhombic symmetry in the space group Pcab. Its cell parameters were found to be; a = 8.1556(7) Å, b = 17.658(2) Å and c = 23.609(2) Å; the unit cell was made up of eight molecules of UC-781. The molecules formed intermolecular hydrogen bonds between NH and thio groups, and were packed in a herringbone-like structure. The data from X-ray powder diffraction showed that crystalline UC-781 was changed into the amorphous state by co-evaporating it with PVP K30. From differential scanning calorimetry analysis, UC-781 peaks were observed in the DSC curves of all physical mixtures, while no peaks corresponding to the drug could be observed in the solid dispersions with the same drug composition up to the concentration of 50% w/w. The data from FT-IR spectroscopy showed the distortions and disappearance of some bands from the drug, while other bands were too broad or significantly less intense compared with the physical mixtures of the crystalline drug in PVP K30. Furthermore, the results from IR spectroscopy demonstrated that UC-781 interacted with PVP K30 in solid dispersions through intermolecular H-bonding.