Polycystic ovary syndrome (PCOS) is frequently diagnosed hormonal disorder with reproductive and metabolic complications. The most common symptoms include cyst in ovaries, anovulation, insulin resistance, and obesity. Clomiphene citrate, an ovulating agent, is the first-line drug used to treat PCOS. We hypothesized that clomiphene citrate, by stimulating ovarian function, with krill oil used as an oil phase to improve solubility, by addressing PCOS-associated symptoms might be effective in PCOS. Hence, our goal was to target hormonal imbalance along with PCOS-associated symptoms using single formulation. The concentration of water (X1), oil (X2) and Smix(surfactant-cosurfactant mixture) (X3) were selected as independent variables, in a simplex lattice design, from microemulsion area derived from pseuodoternary phase diagram while the globule size (Y1) was selected as dependent parameter. The optimized microemulsion showed good sphericity having 41 nm globule size, 0.32 Poly dispersibility index and + 31mV zeta potential. The optimized microemulsion was further evaluated in-vivo using letrozole induced PCOS rats. Formulation treated group reversed the effect of letrozole on body weight and oestrus cycle in comparison to disease control group (p < 0.001). The formulation was also effective in reducing insulin resistance, cholesterol and serum testosterone level (p < 0.001). The in-vivo results were supported by histopathological studies where formulation treated group showed a marked decrease in the number of cystic follicles and a remarkable increase in the number of growing follicles at variable stages, similar to the normal control group. Thus, the results confirmed that novel krill oil based clomiphene microemulsion may become promising therapeutic choice for treatment of PCOS.

Polycystic ovary syndrome (PCOS) is frequently diagnosed hormonal disorder with reproductive and metabolic complications. The most common symptoms include cyst in ovaries, anovulation, insulin resistance, and obesity. Clomiphene citrate, an ovulating agent, is the rst-line drug used to treat PCOS. We hypothesized that clomiphene citrate, by stimulating ovarian function, with krill oil used as an oil phase to improve solubility, by addressing PCOSassociated symptoms might be effective in PCOS. Hence, our goal was to target hormonal imbalance along with PCOS-associated symptoms using single formulation. The concentration of water (X1), oil (X2) and Smix(surfactantcosurfactant mixture) (X3) were selected as independent variables, in a simplex lattice design, from microemulsion area derived from pseuodoternary phase diagram while the globule size (Y1) was selected as dependent parameter. The optimized microemulsion showed good sphericity having 41 nm globule size, 0.32 Poly dispersibility index and + 31mV zeta potential. The optimized microemulsion was further evaluated in-vivo using letrozole induced PCOS rats. Formulation treated group reversed the effect of letrozole on body weight and oestrus cycle in comparison to disease control group (p < 0.001). The formulation was also effective in reducing insulin resistance, cholesterol and serum testosterone level (p < 0.001). The in-vivo results were supported by histopathological studies where formulation treated group showed a marked decrease in the number of cystic follicles and a remarkable increase in the number of growing follicles at variable stages, similar to the normal control group. Thus, the results con rmed that novel krill oil based clomiphene microemulsion may become promising therapeutic choice for treatment of PCOS.