Design of Novel Controlled-Release Suppositories Containing Polyglycerol Ester of Fatty Acid.

Abstract

A novel controlled release suppository consisting of Witepsol H15 as a triglyceride base and polyglycerol ester of fatty acid (PGEF) has been designed and developed. The addition of PGEF to Witepsol H15 resulted in an increase in the solid fat index (SFI), which is correlated with melting point and apparent viscosity, of the Witepsol H15-PGEF (H15-PGEF) mixed base in a similar manner to the case of Witepsol H15-Witepsol E85 (H15-E85) mixed base. In the in vitro release tests, the release rate of Brilliant Blue from the H15-PGEF mixed base was reduced with increase of PGEF content, indicating that the drug release rate from the H15-PGEF mixed base depended on SFI. The change in the drug release rate from the H15-PGEF mixed base with temperature in release tests ranging from 36°C to 39°C was small, whereas the release rate in the H15-E85 mixed base changed significantly with temperature. These changes in drug release rate with temperature in the H15-E85 and H15-PGEF mixed bases were found to be attributable to the variation of SFI of both the mixed bases. In addition, the change in SFI during storage at 30°C in the H15-PGEF mixed base was relatively small as compared with that of the H15-E85 mixed base. From these results, the H15-PGEF mixed base is expected to be useful for stable controlled release suppositories.