Physico chemical Study of Flavonoid Surfactant Interaction Utilization in Neomycin Topical Formulation

Abstract

Flavonoids are the secondary metabolites widely used in pharmaceutical industries due to their several health benefits. Quercetin and rutin, well known flavonoids possesses various pharmacological properties but the constraints of poor aqueous solubility and impermeability across cell membranes restricts their use in formulation development. Moreover, the rising problem of antimicrobial resistance has also caused a serious threat to human life, thus demanding the urgent need of developing more effective antimicrobial formulations. In view of this, the present research work is focused on studying the physico-chemical behavior of different surfactants (SDS, CTAB, Tween 20 and Tween 80) and flavonoids (quercetin and rutin) in order to determine various types of interactions between them and to obtain the most feasible and thermodynamically stable concentrations for their use in developing pharmaceutical topical formulations. The physico-chemical studies included determination of conductivity, density, surface tension, viscosity and ultrasonic sound velocity parameters. From these studies, various thermodynamic and acoustic parameters were calculated viz. standard enthalpy change (and#61508;Hom), standard entropy change (and#61508;Som), change in Gibbs free energy (and#61508;Gom) of micellization; apparent molar volume (and#61542;v) and compressibility (and#61542;k). The interaction of flavonoids with surfactants was studied in different concentrations of water-ethanol solvent systems i.e. aqueous, water-rich (30% v/v ethanol), ethanol-rich (70% v/v ethanol) and absolute ethanolic concentrations. The thermodynamic, acoustic and viscometric data was obtained at different temperatures (20 oC, 25 oC, 30 oC, 35 oC and 40 oC) in order to study the effect of temperature on micellar systems. Thereafter, spectroscopic techniques (FTIR and 1H-NMR) were used to validate the interactions between surfactants and flavonoids and to identify the exact location of flavonoids in the micellar structure of surfactants. Further, the most feasible concentrations obtained from physico-chemical analysis were utilized in developing an improved neomycin topical formulation through drug combinatorial approach. The formulations were subjected for assessment of physical parameters such as determination of pH, viscosity and spreadability. The drug release profile of the formulations was studied through different mathematical models. After evaluation of all the parameters, two best formulations (NQ-T2 [HE] and NR-T1 [HE]) were selected for antimicrobial evaluation studies against different bacterial and fungal clinical isolates. Among the two formulations, NQ-T2 [HE] showed excellent antibacterial activity against the bacterial strains while NR-T1 [HE] also exhibited promising results when compared with the standard formulations. Overall, this study represents a possible solution to enhance the antimicrobial efficacy of neomycin formulations by combining them with flavonoids through micelles assisted drug combination approach. newline