That's quite a frequent problem. There are several ways to tackle it.

First, check the retention behaviour of both compounds in published methods, this may give you some idea how to select the mobile and stationary phase.

• you can use a wide gradient, say something like 10 to 95 % ACN in the mobile phase. While being the default solution, these methods are prone to contamination problems and baseline instability. To speed up the method, you can use a slow low organic gradient at the beginning, then steep gradient to the region the other drug elutes and slow gradient to the end. It's going to be a quite long run anyway, but with the limited resolution needed, you can potentially use very short (3 to 5 cm column).
• try something else as the stationary phase, C8 or CN modified silica may be better in terms of the difference in retention. While C8 is similar to C18, CN behaves differently and requires some experience.
• if the hydrophobic compound is a base or acid, you may try to slow it down using lipophilic ion pair, such as octadecyl sulphonic acid or trimethyl octyl ammonium, tetrabutylammonium or something like that. C8 with ion-pairing may be a good solution.

HPLC gradient elution with 5 - 95% acetonitrile in water on a reversed-phase column will give you better range, and also the back pressure in any analytical HPLC system will not be a problem.

Additionally to already proposed:

1. Playing with pH of mobile phase to make them closer. If their protonation is not affected then the playing with pH is useless

2. You may try Hilic column

Mobile phase mixture contains 50 % hydrophilic and 50% hydrophobic will give you better seperation. Also check complete solubility of your mixture for better resolution of peaks