Self-emulsifying Delivery System for Improving Biopharmaceutical Performance of a Novel Antitubercular Agent: Formulation Development, Biological Activity and Pharmacokinetic Evaluation

Abstract

A nitroimidazole-derived lead (IIIM-019) was developed as a part of our institutional drug discovery program in the area of tuberculosis. This molecule suffers from poor aqueous solubility and to overcome this limitation, lipid-based self-emulsifying drug delivery system (SEDDS) was developed. The SEDDS was characterized for emulsification efficiency, droplet size, stability and drug release. The morphology of SEDDS was investigated by transmission electron microscopy (TEM). The cellular uptake of formulation was assessed in Caco-2 cells and anti-tubercular activity was evaluated in M. tuberculosis H37Rv. Further, the pharmacokinetic profile of formulation was investigated in Balb/C mice. The optimal formulation, F2, was selected based on clarity, particle size, and stability. Characterization studies confirmed that F2 possessed favorable attributes, including a particle size of 120.6 ± 0.7 nm, and thermodynamic stability. The dissolution study revealed significantly enhanced release profile of IIIM-019 from SEDDS compared to its native form. The developed formulation showed uptake in Caco-2 cells and it also exhibited significantly improved anti-tubercular activity. Further, pharmacokinetic study indicated higher plasma exposure and decreased clearance than unformulated IIIM-019. The developed SEDDS formulation increased solubility, dissolution, plasma exposure, and therapeutic effectiveness of IIIM-019, representing a promising carrier for oral administration of investigated anti-tubercular lead.