The release of a drug having low solubility in a certain pH range from controlled-release microspheres using tetraglycerol pentastearate and tetraglycerol monostearate in combination as the matrix base showed pH dependence. Trepibutone, an acidic drug having lower solubility in an acidic medium, was released pH-independently from the microspheres which incorporated magnesium oxide, a solid base. It might have resulted from the pH inside the matrix being kept in an optimum range for drug release due to the incorporation of a solid base. On the other hand, the addition of water soluble acidic or basic excipients was ineffective to achieve pH-independent release. For papaverine, a basic drug, pH-independent drug-release characteristics could be achieved by adding Eudragit L100-55, an enteric polymer. It is thought that the enteric polymer increased the pores for drug release by dissolving in a higher pH range, where the solubility of papaverine is low, and thereby made the release pH-independent. Further, selecting a polyglycerol ester of a fatty acid with an appropriate hydrophile-lipophile balance as the matrix could yield a drug with the desired release rate at any pH.