Vaĭnshteĭn V A, Etingov E D, Naumchik G N
Antibiotiki. 1976 Aug;21(8):679-85.
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.
多烯抗生素与聚乙烯吡咯烷酮（PVP）的复合物可用于制备可溶于水且由精细分散体组成的有效药物剂型。已开展相关研究；这些研究对于揭示多烯与中性聚合物的相互作用机制以及药物剂型生产工艺的开发具有重要意义。在二甲基甲酰胺 - 乙酸乙酯体系中沉淀过程中，获得了分子量为10000和35000的PVP在制霉菌素和两性霉素B上的吸附等温线。计算了复合物中抗生素与聚合物结合强度的常数。结果表明，复合物强度随体系中沉淀剂相对量的增加而增大。研究了结合强度常数的温度依赖性。复合物形成过程显示为放热过程，每摩尔抗生素的复合物活化能为26 - 30千卡。未观察到制霉菌素和两性霉素B结合强度的显著差异。基于实验数据，提出了一种复合物结构示意图，通过抗生素羟基与PVP叔酰胺基团之间形成多个氢键来解释结合过程。
