A General Route for Nanoemulsion Synthesis Using Low-Energy Methods at Constant Temperature

Area of Science:

• Colloid and Surface Science
• Materials Chemistry
• Pharmaceutical Sciences

Background:

• Traditional low-energy nanoemulsion formation relies on the emulsion inversion point (EIP) method, typically involving water addition to oil-surfactant mixtures for O/W systems.
• This established protocol assumes a universal order of mixing, potentially limiting the scope and efficiency of nanoemulsion synthesis.

Purpose of the Study:

• To challenge the universality of the conventional emulsion inversion point (EIP) method for nanoemulsion formation.
• To propose a more generalized methodology for synthesizing both oil-in-water (O/W) and water-in-oil (W/O) nanoemulsions using low-energy approaches.
• To investigate the critical role of surfactant migration in successful nanoemulsion synthesis.

Main Methods:

• Investigated the effect of mixing order on nanoemulsion formation across various model systems.
• Studied the relationship between droplet size and surfactant hydrophilic-lipophilic balance (HLB).
• Analyzed surfactant migration dynamics during the formation process.

Main Results:

• Demonstrated that a reverse order of mixing can be superior to the conventional method for specific surfactant and liquid phase combinations.
• Identified surfactant migration from the initial phase to the interface as a key factor for successful nanoemulsion synthesis.
• Successfully applied the reverse mixing strategy for pharmaceutical drug crystallization and formulation, and alginate-based nanogel synthesis.

Conclusions:

• The order of mixing is a critical, yet often overlooked, parameter in low-energy nanoemulsion formation.
• A generalized methodology accounting for surfactant properties and mixing order enables broader applications of nanoemulsion technology.
• This work opens new avenues for nanoemulsion synthesis and formulation, particularly for pharmaceuticals and nanostructured materials.