The objective of this study was to optimize and develop fast disintegrating liquisolid compact of sertraline hydrochloride to enhance the dissolution and study the dissolution in different pH conditions. Fast disintegrating liquisolid compacts were prepared from Neusilin US2 as a carrier material, Aeroperl 300 as a coating material, crospovidone as a superdisintegrants and Tween80 as a non-volatile liquid vehicle. In liquisolid formulations the ratio of carrier to coating material was kept enhancing. The ratio 40 gives optimal results relative to other ratios. The pre-compression evaluation includes: flow properties, angle of slide and FT-IR study for drug-excipient compatibility. The post-compression evaluation which includes: friability, hardness, wetting time, in-vitro disintegration... time, drug content and % drug release-1 h. Among the superdisintegrants, crospovidone was found to be best to give the fastest disintegration. The optimized batch (F7c) was prepared using 5% crospovidone, shows the shortest disintegration time (44 sec), superior drug release profile (almost 90% drug release). Selected formulation minimizes the pH effect on dissolution. Complete solubilization of drug into non-volatile liquid, provides enhanced drug release due to an improved surface area, wettability and drug solubility.