Percutaneous absorption of valproic acid and its plasma concentration after application of ointment

Abstract

In order to develop a percutaneous (p.c.) dosage form of valproic acid (VPA), ointments containing VPA and both VPA and its calcium salt (VPA-Ca) were prepared. The p.c. absorption was studied by determining the plasma concentrations of VPA in rabbits following application of either ointment. In addition, the in vitro penetration study with excised full-thickness rabbit skin was done to evaluate the pharmaceutical availability. VPA was readily and rapidly absorbed through the skin from the gel ointment. The plasma concentrations of VPA higher than 30 (μg/ml were maintained for 6 h after application of 5% VPA, 5% VPA-Ca gel ointment, and for 4 h after application of 5% VPA ointment. The bi-oavailability of VPA following dosing of both ointments was above 97%. The in vitro penetration rate through the skin and skin/solvent partition coefficient were significantly lower with 5% VPA, 5% VPA-Ca solution than with 5% VPA, suggesting the slower penetration of VPA from the 5% VPA, 5% VPA-Ca. A small difference was observed in the release rate of drugs from these ointments. The present results demonstrated the pharmaceutical effectiveness of the VPA, VPA-Ca ointment for seizure disorders. © 1987, The Pharmaceutical Society of Japan. All rights reserved.