The influence of subcoat application and micro-environmental pH on the dissolution properties of enteric coated
sodium valproate pellets was investigated. The pellets were prepared by
solution-layering or wet-mass extrusion-spheronization methods. In order to pass the USP enteric test, the
solution-layered and wet-mass extruded pellets required 35 and 25%
weight gain of
Eudragit L 30D-55, respectively. The application of a subcoat of either Methocel-E5 (HPMC) or
Opadry AMB to the pellets resulted in a delay in
sodium valproate release in 0.1N HCl. Further delay in drug release was observed when
citric acid was present in a HPMC subcoat or when added to the core pellet formulation. The amount of
drug released from coated pellets was a function of the level of
citric acid in the pellet core or subcoat and subsequent micro-environmental pH of the pellets.
Citric acid exerted a plasticizing effect on the enteric
polymer film and improved film formation and
polymer coalescence. When greater than 10% (w/w)
citric acid was present in the pellets, a decrease in
drug content was observed due to the conversion of
sodium valproate to the volatile compound,
valproic acid. Pellets containing less than 10% (w/w)
citric acid maintained potency during processing.