3D printing of partially-coated floating systems for controlled release of drugs into the stomach

This work focused on the development of a retentive drug delivery system (DDS) able to float in the gastric fluids and to ensure prolonged release of drugs over a pre-defined period of time, being then safely emptied from the stomach. To this end, the design step played a pivotal role. The device was thus devised to be composed of a polyvinyl alcohol-based matrix with a tapered geometry, which was partially coated with an insoluble layer of thermoplastic elastomer. This way, release of allopurinol (ALP), used as model drug, could occur only from the uncoated surfaces, while the peculiar geometry of the hydrophilic swellable/erodible matrix was intended to balance the increase in the diffusional path over time with a wider release area. In addition, the coating featured air pockets, whose volume was sized to compensate for the weight force of the DDS once immersed in gastric fluids, thus ensuring its long-lasting buoyancy. By easing the entrance of gastric fluids when the matrix is completely exhausted, such air pockets would also favor sinking and removal of the DDS from the pylorus. Given the multi-layered geometry of the final floating device, including hard-to-fabricate details (e.g. uncoated surfaces, voids), fused deposition modeling 3D printing was identified as the technique of choice for its effectiveness in manufacturing complex shapes. Various formulations were tested for fabricating both the inner matrix and the outer coating, assessing their thermo-mechanical properties, printability and release behavior. The gastro-retentive system demonstrated prolonged buoyancy (> 12 h) and a wide portfolio of ALP release performances, differing in rate and duration, which would make it a promising platform for personalized delivery of drugs in the upper gastrointestinal tract.