Losartan potassium is an angiotensin II receptor antagonist readily absorbed from the GIT, following oral administration. It has low bioavailability as it undergoes extensive first pass metabolism and low elimination half-life. The present study was aimed at studying sustained release behaviour of the drug using hydrophilic and hydrophobic polymers and to optimise using a 32 full factorial design. Eudragit and HPMC were used to evaluate the effect of hydrophilic and hydrophobic polymers on the release pattern of the drug. A full factorial was implemented at 20, 30 and 40% concentration of hydrophilic polymer and 2.5, 5 and 7.5% of hydrophobic polymer correlating with the release behaviour. Process variables were investigated and the results showed excellent adaptability in releasing drug over prolonged periods. Based on the results, it was found suitable to formulate a dosage form using optimum concentration of hydrophobic polymer along with hydrophilic polymer to vary the release behaviour for over 12 hours.