Enhanced Transdermal Delivery of Apremilast Loaded Ethosomes: Optimization, Characterization and In Vivo Evaluation

Abstract

The low aqueous solubility and permeability of apremilast restricted its clinical efficiency in oral therapy for psoriasis arthritis. This research aimed to develop nanosized lipid carrier with high payload and can provide greater transdermal flux in an attempt to enhance the clinical efficiency of apremilast. Apremilast loaded ethosomes were efficiently formulated by a single-step injection technique. A 33 statistical Box-Behnken experimental design was employed to identify the optimum desirability of ethosomes by assessing the effect of three formulation components (soy lecithin, ethanol and apremilast) on responses such as vesicle size, drug entrapment and transdermal flux. The optimized ethosomes were formulated into a gel and evaluated for in vitro and in vivo characteristics including drug release, permeation and pharmacokinetics in rats. The optimization results indicated a significant effect (p < 0.05) of all three formulation variables on the responses evaluated. Optimized ethosomes exhibited spherical shape, nano-size with good payload and greater transdermal flux. The developed ethosomal gel had good physicochemical and rheological properties suitable for topical application and exhibited prolonged drug release by Weibull diffusion. A short lag time and higher transdermal flux (~4 folds higher than control, p < 0.0001) noticed with ethosomes indicates rapid and greater diffusion through the skin barriers. Pharmacokinetic results demonstrated the potential of ethosomes in the transdermal therapy of apremilast as evidenced by the extent of absorption (AUC0-24, p < 0.0001) when compared with the oral counterpart. In nutshell, the data presented here establish the practical feasibility of ethosomal transdermal delivery and can be an alternative option for oral therapy in treating psoriasis arthritis.