Preparation of sustained-release suppositories of indomethacin using a solid dispersion system and evaluation of bioavailability in rabbits.

Abstract

Sustained-release suppositories of indomethacin (IM) were prepared by the use of a solid dispersion system. As the suppository base, we used a solid matrix of polyethylene glycol 2000(PEG) as a water-soluble carrier and hydroxypropylmethylcellulose phthalate (HP55) as a poorly water-soluble carrier. It was observed by X-ray diffractometry that IM was uniformly dispersed in amorphous state in the matrix suppositories. The rectal administration of 20% HP55 matrix suppositories (M-20-5) in rabbits resulted in both fast-release and sustained-release characteristics as well as good bioavailability. The sustained release of IM from the matrix suppositories was attributed to the formation of a network structure of HP55 which dissolved more slowly than PEG.