Development of ginger extract-loaded self-nanoemulsifying drug delivery system for enhanced solubility of ginger extract

Abstract

The well-known medicinal plant ginger (Zingiber officinale Roscoe) has numerous health benefits, but its key bioactive compound, 6-gingerol, suffers from poor water solubility and stability. This study aimed to enhance the oral delivery of ginger extract by formulating a self-nanoemulsifying drug delivery system (SNEDDS) using a design of experiments (DoE) approach. Ginger rhizomes were extracted by ultrasound-assisted extraction, with a 10-min extraction time yielding the highest 6-gingerol content. An I-optimal mixture design was then applied to develop SNEDDS formulations using castor oil, Cremophor RH40, various co-surfactants (Span 20 or Span 80), and co-solvents (polyethyleneglycol 400 (PEG 400) or ethanol). The optimized SNEDDS readily self-emulsified in gastric medium, producing nano-sized droplets (42.5-78.1 nm) with low polydispersity (0.12-0.58) within 10 min. The ginger extract-loaded SNEDDS (G-SNEDDS) achieved high encapsulation efficiencies, exceeding 90% for both 6-gingerol and 6-shogaol, and significantly enhanced the in vitro release of 6-gingerol, reaching cumulative release levels of approximately 90-100% over 48 h, compared to only 67% from the unformulated extract. Transmission electron microscopy (TEM) confirmed the formation of uniform, spherical nanoemulsion droplets. Short-term stability testing indicated that the optimized formulation remained physically stable, as evidenced by minimal changes in droplet size, and preserved most of the 6-gingerol content under ambient storage conditions; however, exposure to elevated temperatures accelerated the conversion of 6-gingerol to 6-shogaol. Overall, the optimized SNEDDS significantly enhanced the solubility, dissolution, and storage stability of ginger extract, offering a promising strategy to improve the oral bioavailability of the therapeutically active constituents present in ginger.