Semi-solid extrusion 3D printing of pediatric acetazolamide formulation: Impact of the spatial arrangement of extruded material on quality attributes.

Three-dimensional printing has emerged as a transformative technology in pharmaceutical manufacturing, enabling the production of individualized dosage forms. Considering all 3DP techniques, semi-solid extrusion (SSE) stands out in comparison to others. However, the influence of spatial material arrangement on the critical quality attributes (CQAs) of printed dosage forms remains poorly understood. This study aims to quantify the impact of the spatial arrangement of extruded material, infill density and area-to-volume ratio on the CQAs of SSE 3D-printed formulations. Acetazolamide (AZM) printlets were manufactured using a M3DIMAKER 3D printing platform, varying important structural parameters to assess their effect on product performance. A generalized linear model with a Quasi-poisson link function was applied to quantify the contribution of each factor to the final dosage form characteristics. Statistical analysis revealed that infill density had the most significant impact on CQAs, with higher densities improving mechanical strength but prolonging disintegration time. The solid bottom shell increased variability, leading to inconsistencies in weight distribution and dissolution profiles, whereas the shell wall had a minor effect on disintegration and release but contributed to structural integrity. Drug release was significantly influenced by infill density, while the surface area-to-volume ratio showed no strong correlation with dissolution behaviour. This study provides a quantitative assessment of how spatial material distribution in SSE 3D printing affects the CQAs of printed dosage forms. The findings highlight the need to optimize structural parameters to balance mechanical stability and dissolution characteristics, ensuring pharmaceutical compliance.