A new Single Core Osmotic Pump (SCOP) tablet which osmotically delivers high doses of low solubility drug Sertraline Hydrochloride (SET) has been developed. The formulations were compared based on six comparative parameters namely, Q24(total release after 24hr), Q12(total release after 12hr),TL (lag time), RSQzero12 (R square of zero order equation for drug release in 12hr), RR12 (in vitro release rate for 12 hr) and T80%(time require to deliver 80% of drug). The drug release profile from osmotic devices showed that the type of polymer and concentration in the core formulation can markedly affect the drug release. Increasing the amount of osmogent to an optimum level significantly increased Q12 and improved zero order release pattern of SET. Bioavailability enhancing additive, citric acid was added in core formulation, which has multifunction property like enhanced SET solubility, create osmotic pressure difference, act as flux regulating agent and make SET containing composition more hydrophilic. As a result, TL and T80% were decreased and Q12 and RR12 were increased. Increasing concentration of PEG 4000 in the semipermeable membrane of the SCOP markedly decreased TL, T80% and increased Q12, Q24 and RR12. Optimum aperture diameter for the formulations was determined to be 850 µm for zero order release pattern. This study also revealed thatoptimization of SPM thickness is very important for approaching zero order kinetics.The developed SCOP system could be effective to formulate a single layer osmotic controlled release tablet of water insoluble drug with large dose.