Novel lipid-based nanocarrier of nitrofurantoin for improved oral bioavailability and reduced variability in absorption

Abstract

The current research aims to improve oral bioavailability, reduce the variability in absorption, and decrease GI intolerance of Nitrofurantoin (NFT) by presenting in a lipid-based liquid self-nanoemulsifying drug delivery system (L-SNEDDS). L-SNEDDS formulations were developed using a thermosolvency technique. Physicochemical properties including in-vitro drug diffusion were exercised to optimize the formula, further, comparative ex-vivo permeability, in-vitro cell line, in-vitro anti-microbial, and in-vivo pharmacokinetic evaluation of optimized formulation was carried out. Based on the highest saturation solubility, soybean oil, oleoyl polyoxyl-6-glycerides, and diethylene glycol monoethyl ether were selected as oil, surfactant, and co-surfactant, respectively. A Smix ratio of 1:2 was selected based on pseudoternary phase diagrams. The formulation prepared with an equal ratio of oil and Smix exhibited the lowest globule size (59.4 ± 0.8 nm), optimum zeta potential (−21.3 ± 1.1 mV), and faster drug release (95.4 ± 4.2 % in 30 min), and hence was selected for further evaluation. Optimized formulation (SF5) was found stable and showed improved membrane permeability against pure drug suspension (1.84 times) and marketed suspension formulation (1.15 times). SF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. However, it showed the highest zone of inhibition against both the gram-negative and gram-positive organisms. The relative bioavailability of NFT-loaded L-SNEDDS was enhanced by 1.46 and 1.55 times compared to the marketed and pure drug, respectively. Thus, it can be concluded that the variability of oral absorption is minimized, and oral bioavailability is improved by the novel lipid-based nanocarrier system of NFT.