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Background and Importance Proton pump inhibitors (PPIs) are commonly administered via feeding tubes. Their gastric delivery may cause drug degradation, while narrow jejunal tubes risk blockage. Identification of all factors affecting administration and their optimisation is essential for safety and therapeutic efficacy.Aim and Objectives The study aimed to evaluate the feasibility of delivering different PPI formulations via various jejunal access devices by assessing physical compatibility, transit through tubes of different diameters, and the effect of different media on formulation integrity and flow.Material and Methods Several marketed PPI formulations, including omeprazole, pantoprazole, esomeprazole, and lansoprazole, as enteric-coated tablets or pellet-filled capsules, were tested. Pellets were suspended in apple juice or sucrose syrup, while tablets were crushed and/or dispersed in normal saline or 8.4% sodium bicarbonate solution. Administration was simulated using nasojejunal, PEG-J, and jejunostomy tubes (6Fr–20Fr). The fraction of formulation delivered and the incidence of tube obstruction were used as indicators of administration feasibility.Results Completely unobstructed delivery (100%) was achieved for all tested pellets when administered through 20Fr tubes. High passage efficiency (90–97%) was observed in PEG-J and jejunostomy tubes ≥14Fr but was markedly reduced (0–10%) in low-profile and narrow tubes (≤10Fr). Crushed tablets passed through all tube types without obstruction, although 5–15% dosage loss occurred due to enteric coating damage. Sodium bicarbonate improved tablet dispersion compared with saline, while apple juice facilitated pellets flow. Suspensions of pellets in viscous sucrose syrup resulted in almost complete delivery (~100%) through wider tubes.Conclusion and Relevance Crushed enteric-coated tablets were the most feasible formulation for jejunal PPIs administration, passing through all tested tube types without obstruction. However, partial material loss and damage to the enteric coating may affect dose accuracy. Enteric-coated pellets frequently blocked narrow and low-profile tubes, limiting their use in clinical practice. Delivery rate strongly correlated with tube size and formulation type.Conflict of Interest No conflict of interest