Preparation and evaluation of a time-controlled release capsule made of ethylcellulose for colon delivery of drugs

Abstract

We have tried to exploit a time-controlled drug release system, a colon delivery capsule made of ethylcellulose (EC). Our colon delivery capsule is consisting of four parts, capsule body, cap, swellable substance and drug container. The cap, body and drug container were made of EC, which was water-insoluble polymer. At the bottom of the body, four micropores were made. The cap has different thickness and as adhered to the capsule body with concentrated EC solution. The drug release mechanism from the capsule was as follows. AL first, as the gastrointestinal fluid penetrates through these micropores, the swellable substance such as low substituted hydroxypropylcellulose(L-HPC) swells gradually. When the cap cannot endure the swelling pressure, the cap disintegrates and the drug in the container is released from the capsule. This release time of the drug from the capsule, namely the lag-time, is utilized for the delivery of drug to the colon. The lag-time was evaluated both in vitro and in vivo experiments using fluorescein as a model drug. In the case of an in vitro experiment, changing the cap thickness could control the release time of the drug. A good correlationship was obtained between the EC cap thickness and the release time of the drug. In the in vivo experiment, we administered these kinds of capsules having different cap thickness were administered to fasted beagle dogs. As an index of the release time of the drug from the capsule, the peak time(Tmax) at which plasmafluor escein level reached to its maximum level was determined. There was a good correlationship between the mean Tmax and the cap thickness. Therefore, we may state that this time-controlled release capsule will be useful for the colon delivery of drugs. © 1995, THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM. All rights reserved.