A Multi‑Stage Oral Delivery Platform Combining Directional Magnesium Propulsion, Dual Effervescent Rupture, and Chitosan‑Mediated Permeation Enhancement: Proof‑of‑Concept Design and Qualitative Evidence

Conventional enteric coatings for acid-labile drugs rely on passive, pH-dependent polymer dissolution. Here we present a multi-stage oral multiparticulate platform designed to replace the synthetic polymer Eudragit L30D by creating a pH-buffering microenvironment within the pellet core intended to actively neutralise gastric acid rather than merely blocking it, while simultaneously providing directional propulsion and chemical permeation enhancement. The design integrates three sequential mechanisms: (1) a magnesium (Mg) half-coat that generates directional hydrogen bubbles for biased propulsion, (2) a dual effervescent core (MgCO3/NaHCO3/citric acid) encased in a low-plasticiser ethylcellulose (ECN50) shell intended to produce CO₂ for pressure-driven rupture and secondary thrust, and (3) a chitosan layer for intestinal mucoadhesion and tight-junction opening. The platform is benchmarked against a conventional L30D-coated omeprazole formulation (acid stage 1.47%, buffer stage 92.68%, assay 100.85%) manufactured at commercial scale at the same facility. Qualitative visual observations confirmed directional H2 evolution, visible CO₂-driven shell rupture, and chitosan mucoadhesion at intestinal pH; the chitosan layer survived both mechanical stages intact. Quantitative acid-stage dissolution testing of the novel pellets is ongoing, and the acid-protection performance has not yet been verified. This proof-of-concept demonstrates the feasibility of integrating active chemical defence, mechanical propulsion, and permeation enhancement within a single pellet, and a staged experimental roadmap for quantifying the mechanical and chemical permeability contributions is presented.