A multi-compartment pulsatile drug delivery system for sequential release: in vitro and in vivo evaluation

This study presents an innovative, structurally engineered, pulsatile oral drug delivery platform that enables programmable, sequential drug release by integrating a structurally engineered three-dimensional (3D)-printed capsular device with conventional immediate-release (IR) tablets. Unlike coating-based or multilayer systems, which suffer from complex manufacturing and inconsistent release profiles, the multi-compartment capsule provides precise and reproducible control over the release timing through simple structural modifications. Each compartment accommodated intact IR tablets, allowing immediate release from the open-window sections and delayed release from the barrier-enclosed compartments. The lag time (Tlag) before drug release can be predictably tuned by adjusting the barrier wall thickness. The system was optimized for esomeprazole and naproxen, for which gastroprotection requires temporally separated exposure. The in vitro dissolution displayed immediate release of esomeprazole and delayed release of naproxen with Tlag of 11.33 ± 1.37 h. Both immediate absorption of esomeprazole and delayed absorption of naproxen were observed following oral administration in beagle dogs. The time to maximum plasma concentration (Tmax) of esomeprazole was 0.67 ± 0.67 h, whereas the Tmax of naproxen was 9.83 ± 2.40 h with a Tlag of 4.75 ± 1.17 h. These findings demonstrate that this modular 3D-printed platform, combined with conventional tablets, provides controlled and sequential drug delivery, thereby supporting patient-tailored therapeutic regimens.