Y. Akiyama et al., PH-INDEPENDENT CONTROLLED-RELEASE MICROSPHERES USING POLYGLYCEROL ESTERS OF FATTY-ACIDS, Journal of pharmaceutical sciences, 83(11), 1994, pp. 1600-1607
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.