[Nystatin and amphotericin B sorption complexes with polyvinyl-pyrrolidone in nonaqueous solvent systems]

Complexes of polyenic antibiotics with polyvinylpyrrolidone (PVP) can be used for preparing effective pharmaceutical forms soluble in water and consisting of fine dispersions. Studies were carried out; they are of great importance for revealing the mechanism of polyen interaction with neutral polymers, as well as for development of the technological processes for production of the pharmaceutical forms. The sorption isoterms of PVP with the molecular weight of 10 000 and 35 000 on nystatin and amphotericin B were obtained in the process of precipitation in the system of dimethylformamide-ethylacetate. The constants of the strength of the antibiotic binding with the polymer in a complex were calculated. It was shown that the complex strength increased with a rise in the relative amount of the precipitant in the system. The temperature dependence of the binding strength constant was studied. The process of the complex forming was shown to be exothermic, the activation energy of the complex being 26-30 kcal per a mole of the antibiotic. No significant differences in the binding strength of nystatin and amphotericin B were observed. On the basis of the experimental data, a scheme of the complex structure explaining the binding process by formation of a number of hydrogen bonds between the antibiotic hydroxyl groups and the PVP tertiaryamide groups is proposed.