Enhancing Microemulsion-Based Therapeutic Drug Delivery: Exploring Surfactants, Co-Surfactants, and Quality-by-Design Strategies within Pseudoternary Phase Diagrams.

Microemulsions (MEs) are homogeneous, isotropic, transparent, and thermodynamically stable mixtures of water, oil, and surfactants. Their unique properties have garnered increasing interest across various fields, including chemistry, pharmacology, biotechnology, and biology. This review aims to provide a comprehensive overview of ME compositions, their macroscopic appearances, and the roles of their essential components - oil, water, surfactant, and co-surfactant - in controlling the nature and stability of MEs. The review highlights the significance of MEs in drug delivery and other applications, highlighting their potential to enhance the solubility, stability, and bioavailability of active pharmaceutical ingredients (APIs). Key factors influencing ME formation, such as the types of surfactants, oils, water, temperature, and various additives, are thoroughly explored. The physicochemical properties of MEs, including small droplet size, large interfacial area, and solubilization capabilities for both hydrophilic and hydrophobic compounds, are discussed about their impact on biological behavior. The present work is an effort to discuss theories and phase diagrams crucial for ME formation, and the strategy of choosing appropriate surfactants and co-surfactants. and the advancements in the preparation and characterization techniques like the shift from visual inspection to advanced spectroscopic phase behavior studies. The work also describes the potential of MEs in drug delivery showcasing the most commonly used ME-based drug candidates as well as excipients highlighting how different excipients influence the release of active pharmaceutical ingredients and the way and quality-by-design approach has been utilized to optimize MEs, providing insights into the systematic design and development to achieve desired characteristics of ME formulations.