For hydrophobic drugs, we cannot do drug loading and release in the PBS, and have to use non-aqueous solvents. So this condition is far from the in vivo.
What solution do you suggest to solve this problem?
You can add a ratio of organic solvent as ethanol or methanol to the buffer. Or using a ratio of surfactant as Tween 20 or Tween 80. I prefer doing a solubility test in different systems to select the best mixture and know the sink conditions for your experiment.