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: 1.05). 12/2010; 65(12):871-6. DOI: 10.1691/ph.2010.0680
Source: PubMed


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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    • "A 1:1 inclusion complex has been predicted between Lc and CDs (Sarkar et al. 1995; Terekhova et al. 2011). The influence of different excipients on this complexation has previously been investigated by our group (Lilletvedt et al. 2010). Further, we have demonstrated that the phototoxic effect of another neutral photosensitizer (i.e., curcumin) could be strongly enhanced by application of a supersaturated solution (Hegge et al. 2012, 2013). "
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    ABSTRACT: Lumichrome, a photodegradation product of riboflavin, is an endogenous compound in humans. The compound is more photostable and a more efficient photogenerator of singlet oxygen than riboflavin. It absorbs radiation in the UVA and blue-light region, which can be an advantage in antibacterial photodynamic therapy (aPDT) of superficial infections. The aim of this study was to investigate the in vitro aPDT effect of various lumichrome pharmaceutical formulations. Solutions of lumichrome (10-5 – 10-3M) were prepared in plain phosphate buffered saline (PBS) or in PBS solutions containing cyclodextrins, DMSO, PEG 400 or polyoxamers (Pluronic®). Supersaturated solutions of lumichrome in PBS were prepared via the cosolvent and solvent evaporation method. Phototoxic effects of selected lumichrome preparations were studied in planktonic Gram-positive (E. faecalis) and Gram-negative (E. coli) bacteria models. The UVA/blue light source emitted mainly in the range 340-440 nm. Lumichrome was up to tenfold more phototoxic against Grampositive than to Gram-negative bacteria. Bacterial eradication was induced after exposure of lumichrome formulations (PBS, PEG 400 and HP CD) combined with 24 J/cm2 UVA/blue light. Increasing the concentration of lumichrome did not enhance the phototoxic effect, probably due to radiation attenuation in the highly absorbing solution (inner filter effect). Cyclodextrins were efficient enhancers of the lumichrome solubility in aqueous solutions, but inhibited the phototoxic effect. The study demonstrates that assuming the use of an optimized formulation, lumichrome has potential as a UVA/blue light photosensitizer in aPDT.
    Pharmazie 09/2015; 70(9). DOI:10.1691/ph.2015.5006 · 1.05 Impact Factor
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    ABSTRACT: Cyclomaltohexaose (α-cyclodextrin) and cyclomaltoheptaose (β-cyclodextrin) as well as their four methyl ether derivatives, that is, hexakis(2,3-di-O-methyl)cyclomaltohexaose, hexakis(2,3,6-tri-O-methyl)cyclomaltohexaose, heptakis(2,3-di-O-methyl)cyclomaltoheptaose, and heptakis(2,3,6-tri-O-methyl)cyclomaltoheptaose were investigated as the additives in the course of enzymatic decomposition of l-phenylalanine catalyzed by phenylalanine ammonia-lyase. Only a few of those additives behaved like classical inhibitors of the enzymatic reaction under investigation because the values of the Michaelis constants that were obtained, as well as the maximum velocity values depended mostly atypically on the concentrations of those additives. In most cases cyclodextrins caused mixed inhibition, both competitive and noncompetitive, but they also acted as activators for selected concentrations. This atypical behaviour of cyclodextrins is caused by three different and independent effects. The inhibitory effect of cyclodextrins is connected with the decrease of substrate concentration and unfavourable influence on the flexibility of the enzyme molecules. On the other hand, the activating effect is connected with the decrease of product concentration (the product is an inhibitor of the enzymatic reaction under investigation). All these effects are caused by the ability of the cyclodextrins to form inclusion complexes.
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    ABSTRACT: Riboflavin (RF), also known as vitamin B2, belongs to the class of water-soluble vitamins and is widely present in a variety of food products. It is sensitive to light and high temperature, and therefore, needs a consideration of these factors for its stability in food products and pharmaceutical preparations. A number of other factors have also been identified that affect the stability of RF. These factors include radiation source, its intensity and wavelength, pH, presence of oxygen, buffer concentration and ionic strength, solvent polarity and viscosity, and use of stabilizers and complexing agents. A detailed review of the literature in this field has been made and all those factors that affect the photo, thermal and chemical degradation of RF have been discussed. RF undergoes degradation through several mechanisms and an understanding of the mode of photo- and thermal degradation of RF may help in the stabilization of the vitamin. A general scheme for the photodegradation of RF is presented.
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