Caracteristicas espectroscopicas de naftifina y terbinafina interaccion con ciclodextrinas y polimeros insolubles de ciclosextrina

Resumen

Naftifine (e)-N-methyl-N-(1-naphthyl-methyl)-3-phenyl-2-propen-lrami ne and terbinafine (e) -N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalene methanamine are antifungal agents of the allylamine class, represented by naftifine, and they are indicated for the treatment of mycoses. The spectrophotometric and spectrofluorimetric characteristics of both drugs such as molar absorptivities, sensitivity of fluorescence, detection limits and quantum yields have been determined in different solvents, in addition, the pKa vàlues of both drugs have been obtained by solubility measurements. Complexation with cyclodextn'ns has been widely used to improve the solubility, bioavailability and stability of pharmaceuticals. For this reason, the interactions in solution between naftifine and terbinafine with cyclodextn'ns have been studied using ultraviolet-visi ble spectrophotometry, nuclear magnètic resonance (1H-NMR), electrospray ionization mass spectrometry (esi-MS) and solubility isotherms. The influence of temperature, pH and drug structure has been analyzed and the stability constants and the thermodynamic parameters associated to complexation have been determined when it has been possible. In general, the stability constants are higher in bàsic medium and for the drug terbinafine. Solid systems containing each drug and the different cyclodextn'ns have been prepared by kneading, coevaporation and coprecipitation methods, their structure has been characterized and the influence on the dissolution rate has been evaluated. The coevaporation method is the best method for preparing the sòlid complexes and the dissolution rates of these sòlid systems are higher than those of the physical mixtures and pure drugs. Finally, sorption studies of the drugs on insoluble epichlorohydrin cross-linked polymers containing b-CD units have been carried out. The sorption process for both drugs is fast and a high percentage of drug is retained, being higher for terbinafine due to a stronger inclusión in the cyclodextrin cavity. In the case of naftifine, the i sosten'c heat vàlues have been determined as a function of the surface coverage, showing that there are two sites of sorption: the cyclodextrin cavities and the polymer network. For terbinafina, the influence of several parameters, such as temperature, drug concentration, TB:b-CD molar ratio and iònic strength have been studied in order to investígate the best conditions for loading the polymer.