Introduction:Epilepsy is a serious neurological disorder. Lamotrigine is an alternative to lithium for the treatment of epilepsy, and its oral bioavailability is 98%; however, its poor aqueous solubility hinders its oral absorption. Among the techniques available to enhance the solubility, dissolution rate and bio availability of poorly soluble drugs, liqui-solid technique is a novel and promising approach. The objectives of the investigation are to formulate, optimize lamotrigine liqui-solid compacts using 23 factorial experiments, validate experimental designs statistically and to compare with the marketed tablets using similarity and difference factors.Materials and Methods:Based on solubility studies tween 20 as nonvolatile liquid, avicel pH 101 as a carrier and aerosil 200 as a coating material were used. Liquid load factor other flow and compression characteristics were determined for different ratios of carrier and coat materials. Suitable quantities of carrier and coat materials were taken, according to the experimental designs other excipients were added, liqui-solid tablets were prepared by direct compression and evaluated. Drug excipient compatibility was determined using Fourier transform infrared spectroscopy (FTIR) analysis. The hardness, disintegration time and T75% were considered for validation of experimental designs.Results:The physicochemical properties of tablets such as hardness (1.5 ± 0.8–4.95 ± 0.96 kg), in vitro disintegration time (40 ± 20–320 ± 25 s) and Friability (0.39 ± 0.5–1.45 ± 0.2% also <1%) possess all the Indian pharmacopoeal requirements. The T75% was calculated and found to be 6.62–22.8 min. The rate of drug release followed first order kinetics. f1 and f2 values indicated the similarity in dissolution profiles between marketed and the optimized formulation and 63.64% similar with that of the marketed fast disintegrating tablets. FTIR studies revealed the absence of drug excipient incompatibility.