Preparation of sustained-release suppositories containing microencapsulated indomethacin and bioavailability of indomethacin in rabbits.

Abstract

The absorption of indomethacin (IM) from suppositories containing surface-modified IM microcapsules (MC) after rectal administration in rabbits was investigated with the aim of producing sustained-release suppositories. The IM-MC were prepared by phase separation of ethylcellulose (EC) from cyclohexane, and the IM surface was modified with a carboxy-vinyl polymer (Hiviswako® 104, HW) by a dry blend technique before encapsulation.As a sustained plasma level of IM was not obtained when IM-MC-containing suppositories which showed a zero-order release profile were administered, the factors affecting the IM absorption, that is, the EC and HW contents in the MC, and the suppository base and type, were investigated. The EC and HW contents in the MC affected the IM release rate but had little effect on the IM absorption. When the IM-MC were directly administered, the IM plasma level was significantly lower than that after administration of the macrogol base suppository containing the IM-MC. The area under the concentration-time curve (AUC) in the case of the Witepsol® base was smaller than that in the case of the macrogol one. The plasma concentration-time curve of the hollow-type suppository showed a lag time, and the Tmax was delayed by 1 h compared with that of the conventional suppository. Thus, it was found that a suitable kind and amount of suppository base and an appropriate suppository type should be selected to prepare sustained-release suppositories containing IM-MC.