A microparticulate dosage form for a highly soluble drug, diltiazem hydrochloride, was formulated with Eudragit RS100 and RL100 using a novel dual polymer technique. A mixture of diltiazem with Eudragit RS100 (low water permeability) in acetone was coacervated into soft polymer microdrops, following which a mixture of diltiazem and RL100 (high water permeability) was added to produce microparticles consisting of both polymers with diltiazem dispersed in the matrix. A second formulation was developed using the same method except using Eudragit RS100 for both steps. For a comparative study, diltiazem, Eudrait RS100 and RL100 were combined together in a single matrix and formulated into microparticles. In vitro drug release profiles using USP paddle dissolution apparatus 2 revealed that dual polymer matrix microparticles containing Eudragit RS100 in the inner and Eudragit RL100 in the outer core exhibit a suitable release profile with an initial release of the drug followed by a plateau level for the test period of 5 h. Differential scanning calorimetric analysis showed no interaction of the drug with the polymers.