Improved bioavailability of raloxifene hydrochloride using limonene containing transdermal nano-sized vesicles

The present investigation was carried out with the aim of optimization of raloxifene hydrochloride-entrapped, limonene containing transfersomes for transdermal delivery. Several formulations were prepared by varying independent variables such as Phospholipid, sodium cholate and limonene while vesicles size, entrapment efficiency and polydispersity index were the dependent variables for Box-Behnken Design. Further, bioavailability assessment of raloxifene in Wistar rats was evaluated after transdermal application and compared with its oral formulation. It was observed that the optimized raloxifene loaded transfersomes formulation showed vesicle size of 107.8 nm, polydispersity index of 0.252 and entrapment efficiency of 90.2% which is close to the predicted values of 114.45 nm, 0.251 and 82.82% respectively generated by the Design Expert software. The TEM image shows the outline and the core of the well identified sealed spherical structure. Confocal laser microscopy study demonstrated that the prepared transfersomes formulation was capable to increase the permeation of probe dye into deeper layer of rat's skin in comparison to the control dye solution. The transdermal flux presented by the transfersomes gel formulation was found to be 13.20 μg/cm2/h whereas the control gel showed the transdermal flux of 2.35 μg/cm2/h across rat skin. Further the in vivo pharmacokinetic study revealed that the relative bioavailability following application of transfersomes gel in Wistar rats was found be increased by 2.71 times as compared to the oral suspension of raloxifene. It was concluded that the prepared transfersomes formulation was found to be a potentially useful drug carrier for the enhancement of raloxifene bioavailability in rats.