Lumichrome complexation by cyclodextrins: influence of pharmaceutical excipients.

Department of Pharmaceutics, School of Pharmacy, University of Oslo, P O Box 1068 Blindern, 0316 Oslo, Norway.
Pharmazie (Impact Factor: 0.96). 12/2010; 65(12):871-6. DOI: 10.1691/ph.2010.0680
Source: PubMed

ABSTRACT Complexation of the model drug lumichrome by 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD), the most widely used cyclodextrin derivative in pharmaceutical preparations, was investigated in this study. The influence of frequently used pharmaceutical excipients, i.e. alcohols (ethanol, glycerol, propylene glycol), buffers (phosphate, citrate) and tonicity modulators (NaCl, MgCl2) was evaluated by phase solubility, absorption and fluorescence emission spectra and fluorescence lifetime studies. Further, complex formation constants and fluorescence quantum yields were calculated. The formation of a 1:1 complex was indicated by phase solubility studies. The shape of the absorption and emission spectra for lumichrome was nearly independent of dissolution medium. The intensity of the absorption peak was slightly decreasing by the addition of HPbetaCD, which indicates formation of an inclusion complex of lumichrome in the ground state. The intensity of the fluorescence emission peak (i.e. fluorescence quantum yield) was also steadily decreasing by the increase in HPbetaCD concentration. Monoexponential fluorescence decay was obtained in the absence of cyclodextrin. In the presence of cyclodextrin, bi-exponential decays were observed in all aqueous vehicles with the exception of plain water or samples containing salts. The longest decay time corresponds to the lifetime of free (uncomplexed) lumichrome, while the shortest decay time was attributed to the excited state of the complexed alloxazine form of lumichrome. The selected excipients influence the complexation constant and the lumichrome excited state deactivation pathways to various extents.

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    ABSTRACT: Hydrogen bonds were shown to play an important role in the lumichrome photophysics and photochemistry both in solutions and in the solid state. In solutions, lumichrome can form hydrogen-bonded complexes with a variety of molecules, such as acetic acid or methanol, as supported by spectral and equilibrium studies. Photoexcitation of some hydrogen-bonded complexes, having appropriate configuration, as in the case of acetic acid, may lead to excited-state proton transfer, resulting in formation of the isoalloxazinic structure, detectable by its characteristic emission, distinct from that of the intrinsically alloxazinic lumichrome. Theoretical calculations confirmed the role of the hydrogen-bonded complexes, yielding several stable eight-membered cyclic structures of such complexes characterized by spectral changes similar to those observed experimentally. Hydrogen bonds play an essential role in the formation of the lumichrome crystal structure, as follows from the X-ray diffraction results. Interestingly, the crystals studied included molecules of methanol used as solvent in crystal growth. The emission studies of polycrystalline samples, similar to the processes occurring in solutions, point to the importance of hydrogen-bonding interactions in crystal packing allowed by the symmetry of the hydrogen-bonded dimers.
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