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

Abstract

A novel ethylcellulose (EC) capsule which releases drug with a time-controlled fashion has been prepared. This capsule is composed of four parts, drug container, swellable substance, capsule body and cap. At the bottom of the body, micropores are made. As water penetrates through these micropores, the swellable substance such as low substituted hydroxypropyl cellulose (L-HPC) swells. When the cap made of water-insoluble macromolecular substance such as EC cannot persist the swelling pressure, the EC cap disintegrates and the drug in the container is released from the capsule. The lag-time is utilized for the delivery of drug to the colon. The release time of the drug from the capsule was measured both in vitro and in vivo experiments. In the case of an in vitro experiment, after 12mg of fluorescein as a model drug and 238mg of starch were filled into the container, caps having different thickness were attached to the capsule body and release study was performed. The release time of the drug was mainly dependent on the thickness of the cap. Using test capsules of which mean cap thickness were 39.1 +/- 2.3 (SE)microns, 63.1 +/- 5.0 microns and 75.6 +/- 4.1 microns, the in vivo release time was estimated after administration to beagle dogs. As a parameter, the peak time (tmax) when plasma fluorescein concentration reached to its maximum level was determined for the estimation of the release time of the drug from the capsule in the gastrointestinal tract. The in vivo tmax was well correlated with the cap thickness.(ABSTRACT TRUNCATED AT 250 WORDS)