In a trial to delay the release rate of tolmetin sodium from alginate coated microspheres, the use of a copolymer was suggested.  Mixtures of polymers can have a significant property than that of individual polymer to achieve controlled release microspheres.  A 3² factorial design was employed to produce controlled release microspheres of tolmetin sodium in sodium alginate and ethyl cellulose copolymers by emulsification internal gelation methodology. The effect of critical formulation variables namely, drug to polymer ratio(D:P ratio) and speed of rotation on drug loading efficiency (LE), drug release at the end of 2 hours (Rel₂) and drug release at the end of 8 hours (Rel₈) were analyzed using response surface methodology. The parameters were evaluated using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis and analysis of variance.The produced microspheres were spherical in shape with large pores at D:P ratio 1:2 and small pores at drug to polymer ratio 1:4. Differential scanning calorimetry confirmed the stable character of tolmetin sodium in the drug loaded microspheres and revealed crystalinity form.  Both formulation variables studied exerted a significant influence (p < 0.05) on the drug release whereas the speed emerged as a lone factor significantly influencing the drug loading efficiency. Increasing the D: P ratio decreases the release of the drug after two and eight hours. The increase of speed results in an increase of drug release after two and eight hours.  The drug release from the microspheres followed zero order  kinetics.