Design of a controlled release liquid formulation of lamotrigine

ABSTRACT

Lamotrigine is a broad spectrum anticonvulsant drug widely used as mono- or adjunct- therapy in adults and children. The aim of this study was to develop controlled release liquid formulation of lamotrigine to improve bioavailability and compliance of pediatric and geriatric epileptic patients. Multiple [w/o/w] emulsion was prepared using one step emulsification technique. It was evaluated for entrapment efficiency [EE], morphology, zeta potential [ZP], polydispersity index [PI], rheology, thermal property, in vitro drug release behavior and stability. In vivo studies in albino mice were carried out using maximal electroshock seizure [MES] test and strychnine induced seizure [SIS] pattern test and results were compared with marketed formulation. The EE of the formulations varied from 84.37% to 98.11%. The ZP and PI values of the prepared batches were in the range of+23.46 to +28.07 and 0.256 and 0.365, respectively. Microscopic observation clearly indicated the stability of the emulsions during the storage period. All batches exhibited controlled in vitro drug release up to 12 hrs. Batch C11 exhibited significantly longer duration of protection of seizure in mice against MES and exhibited comparable efficacy in SIS as compared to the marketed formulation. Multiple emulsion of lamotrigine compared to the marketed tablet showed plasma drug concentration within therapeutic range for longer time and comparable efficacy