{Reference Type}: Journal Article {Title}: Limitations and Innovative Application Methods of Surfactants for Solubilization of Poorly Water-Soluble Drugs. {Author}: Jin G;Wang J;Xu J;Jin Q;Xue JF;Li LH; {Journal}: Curr Drug Deliv {Volume}: 0 {Issue}: 0 {Year}: 2024 May 29 {Factor}: 3.758 {DOI}: 10.2174/0115672018299592240524074005 {Abstract}: Poor solubility of drugs leads to poor bioavailability and therapeutic efficiency. A large proportion of drugs that are not developed and marketed for use by patients are due to their extremely low solubility. Therefore, improving the solubility of poorly water-soluble drugs is one of the most important aspects of the field of drug research. With the continuous development of more and more formulation techniques and excipient applications, the solubility of poorly water-soluble drugs can be improved to a certain extent to obtain better pharmacokinetics and pharmacodynamics, including pH microenvironment regulation technology, inclusion complex, solid dispersion, nanotechnology, and application of surfactants. However, the most widely used among them is the application of surfactants. This technique can reduce the surface tension, improve wettability, and have a remarkable solubilizing ability after forming micelles. However, surfactants have also been found to possess certain limitations in solubilization. In this review, the factors affecting the solubilization of surfactants and limiting their application have been summarized from several aspects. These factors include drugs, additives, and media. Some ideas to solve these application limitations have also been put forward, which can lay a foundation for the wider application of surfactants in the future.