ORAL DELIVERY SYSTEMS INTENDED FOR COLONIC RELEASE OF INSULIN AND SELECTED FUNCTIONAL ADJUVANTS

Abstract of the PhD thesis entitled “Oral delivery systems intended for colonic release of insulin and selected functional adjuvants” Colon delivery has gained increased attention as a potential approach to improve the oral bioavailability of peptides and proteins. In this respect, the suitability of a previously developed release platform (ChronotopicTM) was explored for the conveyance of insulin and selected functional adjuvants. The system consists of a drug core and a swellable/erodible hydroxypropyl methylcellulose (HPMC) release-controlling coating. When an outer enteric film is applied, colon delivery is obtained based on relatively consistent small intestinal transit time. Preliminarily, the compatibility of insulin with a protease inhibitor (camostat mesilate, CM) and an absorption enhancer (sodium glycocholate, NaGly) was assessed. Subsequently, differing insulin/adjuvants release patterns were pursued by properly modifying the system formulation. A concurrent liberation of these compounds was achieved after reproducible and programmable lag phases from devices in which the protein and enzyme inhibitor/absorption enhancer were included in the core unit. The possibility of timing the adjuvant release to occur prior to that of the protein, which might allow a more favorable environment to be established in advance, was then investigated. For this purpose, prototypes with a CM/NaGly interlayer enclosed between HPMC coatings with differing thicknesses were prepared that elicited flexible two-pulse release profiles.