Parkinsonism is a progressive neuro degenerative illness which can be characterized by tremor, bradykinesia, rigidity, and postural instability. The effect of the Parkinsonism disease reaches 1-2% in people over the age of 50. The symptoms of Parkinsonism disease are largely related to progressive loss of dopamine in the basal ganglia. Parkinson's disease can't be cured, but medications can help control your symptoms, often dramatically. Entacapone is a Catechol-O-methyltransferase (COMT) inhibitor which is the primary medication from this class. This medication when given in combination with levodopa, mildly prolongs the effect of levodopa therapy by blocking an enzyme that breaks down dopamine. The short half life of entacapone necessitated for fabricating entacapone sustained release matrix tablets to provide a therapeutic amount of drug and maintain the desired drug concentration. The objective of the present investigation was to develop Entacapone sustained release matrix tablets using various grades of HPMC K4M, K15M and K100M grades. Drug excipient compatibility of formulations was characterized by FTIR and DSC study and confirmed that no incompatibility was found.