Drug absorption through mucosal membranes: effect of mucosal route and penetrant hydrophilicity.

The influence of mucosal route and penetrant hydrophilicity on the in vivo absorption of a model lipophilic compound, progesterone, was investigated in ovariectomized rabbits. The absorption rate and systemic bioavailability of progesterone and its monohydroxy, dihydroxy, and trihydroxy derivatives were evaluated and compared following oral, nasal, rectal, and vaginal administrations. Nasal delivery resulted in a significantly higher rate and extent of progesterone absorption than oral, rectal, or vaginal administration. The rate and extent of mucosal absorption decreased as penetrant hydrophilicity increased for the nasal, rectal, and vaginal routes. The results of this investigation indicate that the absorption characteristics of a lipophilic compound, such as progesterone, are influenced by the properties of both the mucosa and the drug.