Amino acid derivatives and surfactants as multifunctional excipients for overcoming drug solubility and permeability challenges.

Amino acid derivatives and surfactants are gaining increased application in formulation design due to their unique properties such as biocompatibility and ability to form molecular interactions. This review delves into the emerging role of amino acid derivatives for overcoming drug solubility and permeability challenges, assessing their mechanisms and potential in formulation design. Drug solubility is enhanced by amino acid derivatives and surfactants through several mechanisms such as micelle formation, ion pairing, and hydrotropy, while the transcellular uptake, transporter activation, and prodrug formation enhance permeability. The article summarizes the scope of Gemini amino acid-based surfactants (AAGSs), which have lower critical micelle concentration (CMC), higher solubilization, strong surface activity, better bioavailability and improved stability due to their advanced dimeric amphiphilic features. Beyond solubility and permeability enhancement, future research may aim at optimizing amino acid derivatives for targeted delivery, exploring synergistic effects with nanotechnology, including smart surfactants, nanocarrier systems and targeting neurodegenerative diseases. Overall, amino acid-based systems offer a promising platform for circumventing bioavailability limitations.