Box-Behnken Design-based formulation optimization and characterization of spray dried rutin loaded nanosuspension: State of the art

Abstract

Plant secondary metabolites possess excellent antioxidant properties and reported as important source of antioxidants in nutraceuticals. Rutin is one of the plant secondary metabolites having excellent antioxidant property. It is majorly present in tobacco, rue, buckwheat as well as some citrus fruits such as grapes, lime, orange, buckwheat and lemon. As nutraceutical it is useful in treating osteoporosis, oxidative stress, inflammation, cancer and diabetes. However, its therapeutic efficacy is limited due to its lipophilicity that further causes dissolution rate limited oral bioavailability. The present study deciphers the formulation of nanosuspension loaded with rutin using Box-Behnken Design. The nanosuspension was prepared by media milling using sodium lauryl sulphate as surfactant and hydroxypropyl methyl cellulose K4M as polymer. The ratio of surfactant to rutin, ratio of polymer to rutin, milling time and milling speed were varied as per design to control the particle size and zeta potential. The nanosuspension was then spray dried. The optimized formulation showed particle size, zeta potential and drug loading as 121.24 ± 5.22 nm, -32.83 ± 1.34 mV and 97.66 ± 3.33%, respectively. The results of dissolution and permeability studies showed about 7.5 folds enhancement in dissolution rate and 5.44 folds enhancement in permeability of rutin upon loading into nanosuspension as compared to raw rutin. Upon testing the formulation on Caco2 cells for permeability studies, more than 90% cell were found viable, indicating that the formulation was non-toxic and safe for oral use. The results of powder diffraction (PXRD) revealed unchanged crystallinity of formulation before and after milling, indicating no alteration in crystallinity of drug. The formulation was found stable under accelerated condition of 40 °C/75% relative humidity as indicated by non-significant change in results of particle size, zeta potential, and drug loading of fresh and aged nanosuspension. Overall results indicated successful development of spray dried nanosuspension of rutin.