Polymeric blend microspheres of poly(vinyl pyrrolidone) (PVP) with sodium alginate (NaAlg) were prepared by cross-linking with calcium ions and used to deliver a calcium channel blocker drug, diltiazem hydrochloride (DT). The prepared microspheres were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Scanning electron microscopy confirmed the spherical nature of the particles. Preparation conditions for the microspheres were optimized by considering the percentage entrapment efficiency, particle size, and swelling capacity. Effects of variables such as PVP/NaAlg ratio, molecular weight of PVP, cross-linker concentration, and drug/polymer ratio on the release of DT were discussed at two different pH values (1.2, 6.8) at 37 degrees C. It was observed that DT release from the microspheres decreased with increasing molecular weight of PVP and extent of cross-linking. However, DT release increased with increasing PVP content and drug/polymer ratio (d/p) of the blend microspheres. The highest DT release percentage was obtained as 99% for PVP/NaAlg ratio of 1/2 with d/p ratio of 1/2 at the end of 4 h. It was also observed from release results that DT delivery from the microspheres through the external medium are much higher at low pH (1.2) value than that of high pH (6.8) value. The drug release from the microspheres mostly followed Fickian transport. (c) 2007 Wiley Periodicals, Inc.