Design and development of lipid modified chitosan containing muco-adhesive self-emulsifying drug delivery systems for...

Current study was aimed to design and develop muco-adhesive self-nano emulsifying drug delivery system (SNEDDs) for improved pharmacokinetics of Cefixime (CFX) in rabbits. The components of SNEDDs formulation i.e., cinnamon oil, Tween® 80, and PEG 200 as oil, surfactant, and co-surfactant respectively were selected based on their high solubilizing capability of the drug. SNEDDs formulation was optimized using Design of experiments (D-optimal design) in terms of droplet size, poly dispersity index and zeta potential. The optimized SNEDDs formulation was studied for various parameters like droplet size, morphology, zeta potential, emulsification, optical clarity, thermodynamic stability, GIT stability, and robustness to dilution. CFX was loaded to optimized formulation to form CFX-SNEDDs. Furthermore, acyl-chitosan, a muco-adhesive agent, was added to CFX-SNEDDS to prepare CHT-CFX-SNEDDS. In vitro drug release showed the controlled release behavior reached a maximum value of 70 % at pH 6.8 within 24 h. The droplet size, atomic force microscopy, and optical clarity analysis revealed the formation of nanosized emulsion (156 ± 25 nm) with spherical morphology. Also in vivo pharmacokinetic studies on rabbits showed an increased drug plasma concentration for CHT-CFX-SNEDDs (15 ± 3 μg/mL) and CFX-SNEDDs (9 ± 2 μg/mL) in comparison with control CFX (4 ± 1 μg/mL). The results indicated that the developed CHT-CFX-SNEDDs with an increased degree of solubilization, permeation, and nanosized range emulsion enhance the oral performance of CFX.