The effect of formulation composition and flow conditions on the robustness of semisolid extrusion 3D printing: a case study on poorly water-soluble itraconazole for oral dosage form production

Abstract

Semisolid extrusion 3D printing is a manufacturing method that has shown promising results in precise production of patient specific dosage forms. Drug nanocrystals, where the particle size of the drug is in the nanometer range, is an attractive formulation strategy for improving the bioavailability of poorly water-soluble drugs. However, because nanocrystals remain suspended in the semisolid extrusion 3D printing formulation, dispensing of the material might be adversely affected by these particles. Currently, the effect of suspended drug nanocrystals on the semisolid extrusion dispensing precision is not well understood. In this study, dispensing precision was evaluated by analysing the weight variation during semisolid extrusion 3D printing. The formulation base, where itraconazole nanocrystals and nanofibrillated cellulose were added, consisted of polyethylene glycol, hydroxypropyl methylcellulose, and water. It was discovered that nanocrystals improved the dispensing precision compared to the nanocrystal free formulation base. Additionally, nanofibrillated cellulose could be combined with nanocrystals to improve the dispensing precision even further. The dispensing precision of the formulations was found to be linked with the viscosity at the high shear rate region. In conclusion, the data suggests that drug nanocrystal containing oral dosage forms can be precisely manufactured using semisolid extrusion 3D printing, without major indication of drug nanocrystals adversely affecting the dispensing process.