Targeting the development of 3D printed reservoir-like vaginal rings (VRs) intended to fulfill the needs of precision medicine, prototypes ensuring prolonged release of metronidazole (MTZ) were preliminary manufactured and tested. Indeed, this drug represents the first-line therapy against bacterial vaginosis, which would especially benefit from convenient as well as easy dose adjustment and from more than 48 h continuous release, thus avoiding barely tolerated and repeated administrations. Starting from a soft thermoplastic elastomer (TPE), hollow ring structures were successfully printed at 190 °C and then extemporaneously filled with drug-loaded, in-situ-crosslinking hydrogel formulations based on alginate (ALG). 3 VR designs, differing in dimensions, number of open surfaces as well as in relevant areas were investigated, together with 9 drug-saturated hydrogel formulations containing extra suspended MTZ particles (20-50 %) and increasing ALG concentrations (2-6 %). Manufacturing of final rings was fine-tuned based on materials thermo-mechanical properties. For comparison purposes, hydrogels with analogous composition were either cast using purposely developed molds or 3D printed mimicking the ring design. VR release performance turned out dependent on the drug solubility and on the surface area available for hydrogel contact with vaginal fluids. Interestingly, this surface resulted correlated to both the outer and inner structure of the system. The data collected would provide an effective asset to increase the versatility of reservoir-like VRs, making them a powerful tool towards therapy customization.

In this work, feasibility of injection molding was demonstrated for manufacturing capsule shells. 600 µm-thick prototypes were successfully molded with pharmaceutical-grade low-viscosity polyvinyl alcohols (PVAs), possibly added with a range of different fillers. They showed reproducible weight and thickness (CV < 2 and 5, respectively), compliant behavior upon piercing (holes diameter analogous to the reference), tunable release performance (immediate and pulsatile), and moisture protection capability. To assess the latter, an on-line method relying on near infrared spectroscopy measurements was set-up and validated. Based on the data collected and considering the versatility IM would provide for product shape/thickness/composition, PVA-based molded shells could help widening the portfolio of ready-to-use capsules, representing an interesting alternative to those commercially available. Indeed, these capsules could be filled with various formulations, even those with stability issues, and intended either for oral administration or for pulmonary delivery via single-dose dry powder inhalers.

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 predefined 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 thus 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.

The incorporation of solid particles as a filler to a hydrogel is a strategy to modulate its properties for specific applications, or even to introduce new functionalities to the hydrogel itself. The efficacy of such a modification depends on the filler content and its interaction with the hydrogel matrix. In drug delivery applications, solid particles can be added to hydrogels to improve drug loading capacity, enable the inclusion of poorly soluble drugs, and modulate release kinetics. This work focuses on the case of alginate (ALG)-based hydrogels, obtained following an internal gelation procedure using CaCO₃ as the Ca²⁺ source and containing a high solid volume fraction (up to 50%) of metronidazole (MTZ), a drug with low water solubility, as a potential extrusion-based drug delivery system. The impact of the hydrogel precursor composition (ALG and MTZ content) on the rheological behavior of the filled hydrogel and precursor suspension were investigated, as well as the hydrogel stability and MTZ dissolution. In the absence of solid MTZ, the precursor solutions showed a slightly shear thinning behavior, more accentuated with the increase in ALG concentration. The addition of drugs exceeding the saturation concentration in the precursor suspension resulted in a substantial increase (about one order of magnitude) in the low-shear viscosity and, for the highest MTZ loadings, a yield stress. Despite the significant changes, precursor formulations retained their extrudability, as confirmed by both numerical estimates and experimental validation. MTZ particles did not affect the crosslinking of the precursors to form the hydrogel, but they did control its viscoelastic behavior. In unfilled hydrogels, the ALG concentration controls stability (from 70 h for the lowest concentration to 650 h for the highest) upon immersion in acetate buffer at pH 4.5, determining the MTZ release/hydrogel dissolution behavior. The correlations between composition and material properties offer a basis for building predictive models for fine-tuning their composition of highly filled hydrogel systems.