Novel Expandable Platforms for Gastric Retention

Abstract

Extending the residence time of the drugs with low absorption window is a holy grail in oral drug delivery. If such drug passes the absorption segment, it will be wasted away with no further absorption throughout the gastrointestinal tract. Harsh stomach environment, diet status (fed or fasted), subject to subject variability, stomach motility, dynamic change of the stomach pH, food effect and more are all accounted for a gastric retention program to be very challenging. Although a few concepts including floating, mucoadhesion, swelling and expansion have been utilized in designing gastric retention (GR) platforms, no technology has so far proved to be commercially feasible and therapeutically effective in enhancing the absorption and bio-availability of the drugs with low absorption window. To be effective, a GR platform is expected to stay in the stomach preferably in a fasted state for 6-8 hrs, to release its embedded drug in a controlled manner and finally to disintegrate for a safe removal from the body. Overall, a potential gastric retention platform should generally meet requirements such as pharmaceutical acceptability, mechanical properties, ease of processing and disintegrability. In this project, two novel approaches will be examined to achieve gastric retention. First, a strong platform based on a cryogeling polymer, poly (vinyl alcohol) (PVOH) will be prepared via a freezing-thawing process. Certain factors will be optimized to balance between the platform properties and further processing needs. To make the platform disintegrable, two methods will be used; imprinting weak areas and including extractable particles into the platform base. The platforms will be eventually characterized by mechanical and disintegration (erosion) properties which will be determining their gastric retention potential. Due to its novel nature, the project has a great potential to be patented and licensed to the pharmaceutical industries for further development