A novel disulphide polymer has been synthesised which has been shown to be susceptible to reductive degradation in the colon. The polymer has been coated onto tablets, which have been administered to man. The results from the human testing were extremely encouraging.
A colon-targeted delivery system based on a starch capsule coated with conventional enteric polymers was developed. When this formulation was tested in main, eight out of nine coated capsules disintegrated in the colon. The remaining capsule disintegrated in the terminal ileum.
From studies in rats and a fistulated pig model, an absorption enhancer composition was identified, based on the synergistic effects of two materials. A formulation containing the enhancer and a model peptide encapsulated into a coated starch capsule has been tested in man.
An enteric-coated 5-ASA pellet formulation has been developed. Following extensive in vitro testing, the formulation has progressed to clinical testing in man. Results are awaited.
The availability of the reliable colonic targeting system, based upon biocompatible coating materials, would have a ready route for commercial exploitation in the delivery of conventional drug substances for the local treatment of large bowel disorders.
Improved colonic delivery would also have a major impact on the market for oral controlled release products and more importantly a well conceived system could permit the successful oral delivery of biopharmaceuticals, such as insulin, calcitonin, growth hormone, interferons and colony stimulating factors. Novel biocompatible polymers, that degrade selectively in the colonic region of the human gastrointestinal tract, will be used as coating agents for conventional oral dosage forms so as to provide a delivery system that after oral administration remains intact from mouth to caecum.
The in-vivo disintegration of the device will be triggered by a natural characteristic of the large bowel so as to guarantee the selectivity of the system, ie pre-programmed release. In the case of peptide delivery, it is highly likely that additional performance modifiers (critical components) will have to be added to the formulation in order that satisfactory oral bioavailability can be achieved.
Following the successful completion of the defined research programme, the partners will locate suitable large companies, preferably European, for the commercial exploitation of the final prototype formulations.
20090 Trezzano Sul Naviglio Milano