Non-steroidal anti-inflammatory drugs (NSAIDs) have wide applicability in management of inflammatory and pain related diseases but limited applicability is characterized by common use and gastrointestinal disturbance. Present study is the trying to come up with sustained release (SR) matrix tablets of NSAIDs using hydrophilic and hydrophobic polymers and correlate the results of in-vitro drug release with the in-vivo pharmacokinetics response. The Ibuprofen drug was selected to be the model, and the direct compression of matrix tablet with HPMC K100M and ethyl cellulose was done. The drug was undergone in-vitro dissolution study using USP-II apparatus with phosphate buffer (pH7.2) and during in-vivo pharmacokinetics testing using healthy volunteers approach crossover study. They came up with a favourable Level An in-vitro/ in-vivo correlation (IVIVC) (R 2= 0.987), showing that the in-vitro kinetics of drug released is a fair representation of the average put on plasma. Sustained release matrix has succeeded in prolonging the duration of drug release to 12 hours and reduced Cmax which contributed to reduction of adverse effects related to a peak. These findings encourage studies into establishing the means of developing SR NSAID formulation to assist in GI toxicity and compliance in patients.