Development of a multi-component gastroretentive expandable drug delivery system (GREDDS) for personalized administration of metformin

Objectives: Efficacy and compliance of type II diabetes treatment would greatly benefit from dosage forms providing controlled release of metformin in the upper gastrointestinal tract. In this respect, the feasibility of a new system ensuring stomach-retention and personalized release of this drug at its absorption window for multiple days was investigated. Methods: The system proposed comprised of a drug-containing core and a viscoelastic umbrella-like skeleton, which were manufactured by melt-casting and 3D printing. Prototypes, alone or upon assembly and insertion into commercially-available capsules, were characterized for key parameters: thermo-mechanical properties, accelerated stability, degradation, drug release, deployment performance, and resistance to simulated gastric contractions. Results: Each part of the system was successfully manufactured using purposely-selected materials and the performance of final prototypes matched the desired one. This included: i) easy folding of the skeleton against the core in the collapsed administered shape, ii) rapid recovery of the cumbersome configuration at the target site, even upon storage, and iii) prolonged release of metformin. Conclusions: Composition, geometry, and performance of the system developed in this work were deemed acceptable for stomach-retention and prolonged as well as customizable release of metformin in its absorption window, laying promising bases for further development steps.