Design and development of permeation enhancer containing self-nanoemulsifying drug delivery system (SNEDDS) for ceftriaxone sodium improved oral pharmacokinetics

Ceftriaxone sodium cannot be delivered orally due to its lower permeability and gastric instability. Selfnanoemulsifying drug delivery systems (SNEDDS) spontaneously formoil-in-water nanoemulsions and are preferred for oral drug delivery owing to their enhanced permeation capabilities. This study is based on design and development of permeation enhancer containing SNEDDS for oral bioavailability of ceftriaxone sodium. Cinnamon oil, Tween 80 and propylene glycol were selected as oil, surfactant and co-surfactant respectively for the development of SNEDDS on the base of drug solubility and emulsifying ability. Region of self-nanoemulsification was selected through construction of phase diagram. Optimal formulation with best attributes consisted 43.33%, 30% and 26.77% (w/w) oil, surfactant and co-surfactant respectively. SNAC (Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate)was used as permeation enhancer for the development of SNEDDS. The resultant nano-emulsion was investigated for various parameters and stabilities using zetasizer, atomic force microscope, TGA, DSC, FTIR analysis and dilution and thermodynamic stability studies. It was further screened for cellular uptake and in vivo oral bioavailability of the drug. Drug loaded nano-emulsion revealed negatively charged nano size droplets (166-208 nm) and was highly stable against dilution as well as temperature. Drug remained chemically well intact in solubilized from in oil droplets. The drug cellular uptake and in vivo oral bioavailability remarkably increased upon delivery in permeation enhancer containing SNEDDS. Findings of the study confirm the applicability of the designed SNEDDS for enhancing oral bioavailability of Ceftriaxone sodium.