Nanoemulsion Technology in Oral Drug Delivery: A Path to Enhanced Solubility and Bioavailability

Nanoemulsions (NEs) are submicron-sized colloidal dispersions (20-500 nm) consisting of oil and aqueous phases stabilized by surfactants and cosurfactants. Despite their thermodynamic instability, NEs maintain kinetic stability, preventing separation and aggregation. This stability distinguishes them from microemulsions, which are thermodynamically stable and formed spontaneously. The emulsification process involves a reduction in Gibbs surface free energy facilitated by emulsifiers that lower interfacial tension, crucial for compensating for the high surface area associated with small droplet sizes. The Gibbs free energy reduction is vital as it helps in stabilizing nanoemulsions, while Laplace pressure, resulting from the curvature of the droplets, affects the stability and uniformity of the system. High Laplace pressures in smaller droplets can lead to coalescence, but the proper formulation with suitable surfactants can help mitigate this effect. This review investigates the hypothesis that NEs can significantly enhance the solubility and bioavailability of hydrophobic drugs by optimizing their formulation and stability. We focus on the role of emulsification techniques in creating stable nanoemulsions, with particular attention to the impact of hydrophilic-lipophilic balance (HLB) and critical packing parameters (CPP) on droplet size and stability. Furthermore, we provide a detailed comparison of various preparation methods, including ultrasonication and high-pressure homogenization, emphasizing their influence on droplet size, stability, and scalability. Experimental data from in vitro and in vivo studies illustrate the advantages of NEs for oral drug delivery, with findings showing significant improvements in bioavailability for poorly soluble drugs, such as paclitaxel and curcumin, under optimized formulation conditions. This review highlights the potential of NEs to overcome the limitations of traditional drug delivery systems and provides a roadmap for future research to improve their commercial viability and therapeutic outcomes.