RESUMEN
The biological electron transfer reactions play an important role in the bioactivity of drugs; thus, the knowledge of their electrochemical behavior is crucial. The formation of radicals during oxidation or reduction, the presence of short-living intermediates, the determination of reaction mechanisms involving electron and proton transfers, all contribute to the comprehension of drug activities and the determination of their mode of action and their metabolites. In addition, if a drug is encapsulated in the cyclodextrin cavity, its electrochemical properties can change compared to a free drug molecule. Here we describe the combination of cyclic voltammetry, UV-Vis spectroelectrochemistry, GC-MS, HPLC-DAD, and HPLC-MS/MS as techniques for evaluating the oxidation mechanism of a drug encapsulated in the cavity of a cyclodextrin. The cavity of cyclodextrin plays a significant role in increasing the stability of the encapsulated products; therefore the identification of oxidation intermediates as semiquinone and benzofuranone derivatives of quercetin is possible in these conditions. The differences in oxidation potentials of the bioactive flavonol quercetin and its cyclodextrin complex relating to its antioxidant activity and the oxidation mechanism are herein discussed.
Asunto(s)
Antioxidantes/química , Ciclodextrinas/química , Portadores de Fármacos/química , Técnicas Electroquímicas , Quercetina/química , Espectrofotometría Ultravioleta , Espectrometría de Masas en TándemRESUMEN
The present study was aimed to develop a medium-throughput screening technique for investigation of cyclodextrin (CD)-active pharmaceutical ingredient (API) complexes. Dual-phase potentiometric lipophilicity measurement, as gold standard technique, was combined with the partition coefficient method (plotting the reciprocal of partition coefficients of APIs as a function of CD concentration). A general equation was derived for determination of stability constants of 1:1 CD-API complexes (K1:1,CD) based on solely the changes of partition coefficients (logPo/wN-logPappN), without measurement of the actual API concentrations. Experimentally determined logP value (-1.64) of 6-deoxy-6[(5/6)-fluoresceinylthioureido]-HPBCD (FITC-NH-HPBCD) was used to estimate the logP value (≈ -2.5 to -3) of (2-hydroxypropyl)-ß-cyclodextrin (HPBCD). The results suggested that the amount of HPBCD can be considered to be inconsequential in the octanol phase. The decrease of octanol volume due to the octanol-CD complexation was considered, thus a corrected octanol-water phase ratio was also introduced. The K1:1,CD values obtained by this developed method showed a good accordance with the results from other orthogonal methods.
Asunto(s)
1-Octanol/química , Ciclodextrinas/química , Agua/química , Concentración de Iones de Hidrógeno , Potenciometría , SolubilidadRESUMEN
Infectious diseases are a heterogeneous group of maladies that represent a serious burden to healthcare systems worldwide. Most of the available antimicrobial drugs display poor biopharmaceutical properties that compromise their effectiveness. Cyclodextrins (CDs) are cyclic oligosaccharides of glucopyranose formed by a variable number of repeating units that combine a hydrophilic surface with a hydrophobic cavity. The production of drug/CD complexes has become one of the most extensively investigated technology approaches to improve the stability, solubility, dissolution rate and bioavailability of drugs. The present work overviews the applications of CDs for the formulation of anti-infective agents along with the most relevant administration routes. Finally, an update on the complexes with CDs available on the market to treat infectious diseases is presented.