Formulation and Evaluation of Mixed Micelles Containing Quercetin for Inhibiting Intestinal Metabolism of Atorvastatin

Abstract

Atorvastatin is a poorly bioavailable drug due to fast-pass metabolism. The objective of the study was to prepare quercetin-containing mixed micelles for inhibiting intestinal metabolism of Atorvastatin. Mixed micelles of atorvastatin were prepared using the film hydration method and optimized the formulations were based on different ratios of poloxamer 188 and SDC. The drug permeation and permeability coefficients of mixed micelles were calculated from ex vivo study using goat intestine. To the optimized formulation (F7), quercetin was added to improve the permeability of Atorvastatin. The vesicle size, % entrapment efficiency, and % in vitro drug release of optimized formulation (F7) were found 273.11 nm, 91.34 % and 72.14 %, respectively. The ex vivo results of Atorvastatin with quercetin (25 mg) showed two times more permeation (flux = 2.69 µg/cm2h) and Atorvastatin mixed micelles with quercetin (25 mg) showed three times (flux = 4.33 µg/cm2h ) compared to Atorvastatin without quercetin (flux = 1.34 µg/cm2h). The improvement of Atorvastatin permeation in the form of mixed micelles may be due to the blockage of the p glycoprotein efflux pump in the presence of quercetin. Histopathology study indicated that the formulation changed the microenvironment of tissue when using mixed micelles compared to no significant changes that occurred during control tissue. Based on the obtained results, we can conclude that the mixed micelles containing Atorvastatin enhanced the permeability effect in the presence of quercetin compared to the plain formulation without quercetin.