The liquid−liquid equilibrium of aqueous two-phase systems incorporating polyvinylpyrrolidone with a molecular weight of 10,000 g/mol and lithium sulfate was examined under various temperatures and pH conditions. The impact of temperature and pH on the system's ability to form phases was also explored. The empirical and thermodynamic equations effectively modeled the obtained experimental binodal curves and tie-line compositions. Ciprofloxacin drug partitioning in this system was investigated at temperatures of 298.15, 308.15, and 318.15 K and pH levels of 4.0, 6.0, 7.0, 8.0, and 10.0. The findings revealed that optimal partitioning occurred at 308.15 K and neutral pH conditions.