Naproxen printlets for extemporaneous dispersion: Designing new medicines for drug delivery through the enteral route.

Off-label use of medicines administered via enteral feeding tubes (EFT) can lead to dose inaccuracies, adverse effects and tube obstruction, compromising therapeutic outcomes. Thus, new manufacturing processes are required to design medicines specifically for EFT administration. In this study, a 3D printing semi-solid extrusion (SSE) technique was employed to produce circular-shaped naproxen printlets (P-NPX) (18 × 18 × 2.6 mm, 30 % infill) for aqueous dispersion prior to EFT administration. Mesoporous silica nanoparticles (MSN) were used as NPX nanocarriers for development of printlets (P-NPX-MSN). Results show that MSN drug encapsulation enabled production of printlets with reproducible NPX content, without organic solvents; while providing better shape retention. Aqueous dispersion times were 806 ± 26 s for P-NPX and 813 ± 20 s for P-NPX-MSN. For both formulations, resulting dispersions were slightly acidic (pH ∼ 5), with viscosity of 1.3 cP and particle size distribution that ensured NPX administration without tube obstruction. Drug recovery was ∼ 100 % for both formulations after tube passage. Re-dispersed printlets had reduced vascular event compared to positive controls in Hen's Egg Test - Chorioallantoic Membrane (HET-CAM) assay (in vitro alternative model) and were classified as slight irritants. This study provides an innovative route for drugs presenting gastric irritation, advancing SSE 3D printing for personalised EFT medicines.