| Biorelevant media, such as fasted state simulated intestinal fluid (FaSSIF), are often used to forecast in vivo behavior of oral solid formulations in the gastrointestinal tract. This study uses conventional surfactants (Tween 80 and sodium lauryl sulfate) and a model based on structural parameters (i.e., molecular descriptors) to evaluate possible alternatives to FaSSIF for solubility evaluation of three poorly soluble drugs. The solubility of enrofloxacin, lamotrigine, and phenobarbital was determined in phosphate buffer solution (PBS, pH 6.5) and FaSSIF. The molecular descriptors of drugs were computed, and a mathematical model based on logistic regression was generated to estimate solubilization in FaSSIF compared with PBS. The results demonstrated that solubility of enrofloxacin, lamotrigine, and phenobarbital in Tween 80 (0.1% w/v) was similar to their solubility in FaSSIF, and the proposed model calculated the solubilization ratio with 80% accuracy. In conclusion, Tween 80 in low concentration (i.e., 0.05%) is an appropriate low-cost alternative to FaSSIF, and the proposed model can be used to evaluate the possibility of solubilization in FaSSIF. |