PH-INDEPENDENT CONTROLLED-RELEASE MICROSPHERES USING POLYGLYCEROL ESTERS OF FATTY-ACIDS

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 p H dependence. Trepibutone, an acidic drug having lower solubility in a n acidic medium, was released pH-independently from the microspheres w hich incorporated magnesium oxide, a solid base. It might have resulte d from the pH inside the matrix being kept in an optimum range for dru g release due to the incorporation of a solid base. On the other hand, the addition of water soluble acidic or basic excipients was ineffect ive to achieve pH-independent release. For papaverine, a basic drug, p H-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 o f a fatty acid with an appropriate hydrophile-lipophile balance as the matrix could yield a drug with the desired release rate at any pH.