Semi-solid extrusion 3D printing of plant-origin rosmarinic acid loaded in aqueous polyethylene oxide gels

Context: : Pharmaceutical 3D printing is a promising technology for preparing next-generation patient-specific drug delivery systems (DDSs) for oral administration. Rosmarinic acid (RA) was first isolated from the Rosmarinus officinalis plant, and currently, it is a well-known plant-origin active pharmaceutical ingredient (API) with anti-oxidative, hypoglycemic, antiviral, neuroprotective, and hepatoprotective effects. The therapeutic efficacy of RA, however, is dose-dependent, and it is sparingly soluble in water, which greatly limits the oral administration and bioavailability of this plant-origin API. Aims: : To develop RA-loaded polyethylene oxide (PEO) aqueous gels for semi-solid extrusion (SSE) 3D printing and to investigate the performance of such 3D- printed oral solid DDSs intended for pharmaceutical applications. Methods: : For SSE 3D printing, aqueous PEO gel formulations loaded with RA at different concentrations were prepared, and the physical appearance, homogeneity, and viscosity of the aqueous PEO gels were investigated. Results: : The RA-PEO gels were printed to lattice- and round-shaped solid DDSs with a head speed of 0.5 mm/s, and the weight (mass uniformity) and effective surface area of the printed DDSs were determined. We found that the maximum concentration of RA loadable in the PEO gel for SSE 3D printing was 100 mg/mL. The optimal ratio of RA and surface-active agent (eumulgin) was 1 to 1.5. The key process parameters of the SSE 3D printing were identified and verified. The printing quality of RA-PEO DDSs was very good, thus showing the compatibility of a plant-origin substance and a carrier polymer (PEO). Conclusions: : The SSE 3D-printed preparations obtained from aqueous PEO gels disintegrated rapidly within 15-20 minutes, suggesting their potential applicability as an oral immediate-release delivery system for RA.