About the impact of hydrophilic organic solvents on the emulsifying properties of self-emulsifying drug delivery systems (SEDDS)

Abstract

This study presents the first comprehensive evidence that hydrophilic organic solvents markedly accelerate SEDDS emulsification under biorelevant conditions, while maintaining both stability and safety. These findings establish their critical role as functional excipients in the development of advanced oral lipid-based drug delivery systems. Three different hydrophilic organic solvents benzyl alcohol, ethanol and propylene glycol were incorporated into self-emulsifying drug delivery systems (SEDDS). The emulsification time of SEDDS, with and without these solvents, was evaluated in various media, including demineralized water and HEPES buffer pH 5 and 7.5. Additionally, the stability of the formed oily droplets in the presence of bile salts was assessed based on their size distribution, polydispersity index (PDI), and zeta potential. Furthermore, membrane toxicity of the formulations was tested on human red blood cells (RBCs). Due to the incorporation of 30% benzyl alcohol, ethanol and propylene glycol, emulsification time was 12-fold, 8.2-fold and 5.6-fold accellerated, respectively. Furthermore, SEDDS containing the hydrophilic organic solvents benzyl alcohol and ethanol exhibited no significant change in size distribution, PDI and zeta potential when exposed to bile salts. SEDDS containing benzyl alcohol showed the lowest membrane damaging effect of all tested hydrophilic organic solvents. According to these results, the emulsifying properties of SEDDS can be significantly accellerated by the addition of hydrophilic organic solvents, with benzyl alcohol emerging as the most promising option.