Optimization and Evaluation of Self-nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Plumbagin

Plumbagin, a potential bioactive lipophilic molecule, possesses limited solubility and low oral bioavailability. The purpose of the present study was to examine the potential of the self-nanoemulsifying drug delivery system for improving solubility and oral bioavailability of plumbagin. The self-nanoemulsifying drug delivery system was formulated from Capmul MCM (oil), Tween 20 (surfactant), and propylene glycol (cosurfactant). Central composite design was employed as statistical tool to optimize the formulation variables, X-1(oil) and X-2(surfactant: co-surfactant mixture ratio), of the self-nanoemulsifying drug delivery system. The responses studied were droplet size, self-emulsification time, % of drug release in 15min, and equilibrium solubility. The optimized liquid self-nanoemulsifying drug delivery system was adsorbed on Neusilin US2 and characterized for flow properties, X-ray diffractometry, differential scanning calorimetry, in vitro dissolution, in vivo anti-inflammatory activity, and bioavailability study in Wistar rats, as well as ex vivo permeation study. The droplet size, polydispersity index, self-emulsification time, and equilibrium solubility of the optimized formulation were 58.500 +/- 1.170nm, 0.228 +/- 0.012, 17.660 +/- 1.520s, and 34.180 +/- 1.380mg/mL, respectively. Its zeta potential, transmittance value, and cloud point were -28.200 +/- 1.200mV, 99.200%+/- 0.600, and 90 degrees C, respectively. Drug release was found to be 93.320%+/- 1.090. In vivo anti-inflammatory study confirmed more enhanced activity from the self-nanoemulsifying drug delivery system than with pure plumbagin. Pharmacokinetic study in rats revealed that solid self-nanoemulsifying drug delivery system had 4.49-fold higher bioavailability than pure plumbagin. Ex vivo permeation study demonstrated 1.75-fold increased intestinal permeability of the self-nanoemulsifying drug delivery system than pure plumbagin. The developed self-nanoemulsifying drug delivery system is a useful solid platform for improving solubility and oral bioavailability of plumbagin.

Automated summary

The study successfully improved the solubility and oral bioavailability of plumbagin through a self-nanoemulsifying drug delivery system, which optimized the liquid formulation and demonstrated enhanced performance compared to pure plumbagin, resulting in significantly higher bioavailability and intestinal permeability.