An in vitro controlled release study of valproic acid encapsulated in a titania ceramic matrix

Despite the therapeutic efficacy of valproic acid towards numerous diseases, its poor bioavailability and systemic side effects pose significant barriers to long term treatment. In order to take advantage of controlled release implants of valproic acid, the drug was encapsulated into titania ceramic matrices via a sol-gel process. The integrity and structure of valproic acid-containing matrices were characterized through the use of FESEM, TEM, and BET analyses. In vitro controlled release studies and kinetic analyses were performed under ambient conditions (25 °C, atmospheric pressure) and controlled release behaviors were studied using a GC-MS method. Results showed first order dependence in the rate of valproic acid release as a function of drug concentrations in the titania ceramic device. A marked dependence on the surface area and pore size distribution with drug loading was also observed. This research opens new possibilities for the design of novel time-delayed controlled release systems for valproic acid encapsulates.

► A nanoparticulate TiO2 matrix was loaded with valproic acid (VPA). ► The release of VPA into methanol was monitored over long time periods. ► The kinetics of the release were analyzed. ► Theresults suggest that VPA-TiO2 implants can be used as nanocarriers for the treatment of epilepsy.