This research aimed to evaluate a new approach for preparation of in situ gel and to design innovative peroral delivery systems for Ranitidine Hydrochloride (RHCl) able to enhance the control release. The present study was carried out to optimize and evaluate an oral in-situ gel containing ranitidine HCl with Pluronic F-127 and hydrophilic HPMC E50 by the simple mixing method. The compatibility of the polymers was proved by FTIR. The prepared in-situ gel formulations were tested for their physicochemical characteristics such as clarity, gel strength, gelation temperature, drug content, sol-gel transition time and in vitro release studies of ranitidine HCl-loaded in-situ gel formulation in phosphate buffer (pH 1.2 and 7.4. ) were performed using a modified diffusion cell across dialysis membrane. The prepared formulations were clear and Gel strength ranges from 31±1.6 to 33±1.2. The drug content for the prepared formulations was 97.23% to 99.02%.Then the Drug release at 12 h is 98.25 and thus shown controlled release.