Lipophilic metronidazole derivatives and their absorption through hairlessmouse skin

Previously we have shown that the diacyl glyceryl ester of naproxen is abso rbed into excised mouse skin and slowly degraded to release naproxen. In th e present work we have synthesised some organic acid and fatty acid derivat ives of metronidazole, and studied the in-vitro degradation in aqueous buff er solutions and serum as well as their permeation through hairless mouse s kin. The derivatives were enzymatically degraded in serum to form metronida zole. Only the acetic acid and butyric acid derivatives were able to permea te hairless mouse skin intact. The fatty acid derivatives released metronid azole within the skin. The metronidazole delivery through the skin was sign ificant when the metronidazole oleate was used. This compound could therefo re be considered as a suitable pro drug for dermal applications.