Formulation of Self Nano-Emulsifying Systems of Ezetimibe. Effect of Lipidic Chain Length and HLB of Emulgents on In Vitro, In Situ Perfusion and In Vivo Pharmacodynamic Studies

      Аннотация: Oral route is preferred for the treatment of various diseases/disorders. However, the oral bioavailability of nearly 40% of newly discovered molecules is diminished due to various physicochemical and physiological barriers. The reasons of low and variable oral bioavailability include, high lipophilicity, restricted permeability, first pass metabolism in the gut and liver and efflux transporter systems. These problems, in turn, lead to high intra- and inter-subject variability and lack of dose proportionality. To overcome these drawbacks, various formulation strategies have been adopted. However, the focus has recently shifted to lipid-based formulations owing to their ability to improve the oral bioavailability of poorly water soluble drug compounds. In this regard, self-emulsifying drug delivery systems (SEDDS), particularly nano-based systems, have been able to surmount the above mentioned problems. SEDDS are the recent technological innovations which are physically more stable and easier to manufacture with the globule size ranging between 10 to 1000 nm. Not only this, SEDDS are able to modulate the drug absorption leading ultimately to enhance oral bioavailability.

Ключевые слова: rheology, Central composite design, SNEDDS, Formulation by Design, SPIP, Plasma lipid levels, Bioavailability enhancement