Nowadays pharmaceutical industries and regulatory authorities suggest new approaches such as Quality by Design principles to reduce experiments of formulation studies, improve product quality, save cost and time. SeDeM Expert System is a predictive approach for the preformulation studies and it provides information about suitability of API for direct compression by evaluating 12 parameters. The system also allows selecting appropriate excipients by determining same parameters to improve compressibility of API. The objective of this study was to develop direct compressed memantine orally disintegrating tablets using SeDeM Expert System. Memantine was found to have poor flow and compressibility properties. Three different direct compressibility and super disintegrating agents (Ludiflash((R)), Ludipress((R)) and Parteck((R))) were used to improve compressibility of memantine and according to SeDeM diagrams, Parteck((R)) was selected for final formulation. Memantine direct compressed tablets showed proper friability, hardness and thickness. The disintegration time of the tables were found below 15s which was suitable for ODTs. It was found that SeDeM Expert System was easy to use and application of this method provided to develop memantine direct compressed ODT formulation was successful.