Getting a drug through the skin actually means crossing two very different barriers back to back, a fatty outer layer, then a watery inner layer. A single log P value has to work for both, which is the idea to test each option against.
- Below 1: Too water-loving to dissolve into the fatty stratum corneum in the first place, so the drug barely enters the skin at all.
- 1-3: Lipid solubility here is high enough to move through the fatty barrier, and water solubility is still high enough to continue through the watery dermis afterward, satisfying both legs of the journey.
- 5-7: Fine for entering the fatty layer, but the drug becomes reluctant to leave it and move into the watery tissue beneath, so it piles up in the skin instead of reaching the blood.
- Above 7: Even more extreme lipid-loving behavior worsens the same problem, trapping the drug in fat and blocking systemic absorption almost entirely.
Because the skin presents a fat barrier followed by a water barrier, only a moderate log P value carries a drug across both. The correct answer is 1-3.