Tailored pediatric clonazepam tablets produced by 3D printing: Meeting quality standards and improving permeation

Semi-solid extrusion enables production of personalized and child-friendly tablets from emulsion gels containing lipid-based formulations loaded with poorly water-soluble compounds. While these 3D-printed tablets previously have shown compliance with several pharmacopeia requirements, the impact of gel composition on the tablet characteristics is yet unknown. Therefore, this study aimed to evaluate the relationship between the formulation, drug content and quality attributes using quality by design concepts, with the goal to determine an optimal emulsion gel composition suitable for semi-solid extrusion. The quality by design included to define a quality target product profile, risk assessment of the production line, and design of experiments to optimize the formulation and evaluate the robustness of the obtained design space. In the design of experiments, the impact of the excipient ratios of the emulsion gel on the gel viscoelasticity, tablet mass uniformity and disintegration time were included. The defined design space enabled the quality attribute targets to be reached with low probability of failure. The quality attribute targets were met for the chosen optimal gel, as well as for the optimal gel loaded with clonazepam. 3D-printed clonazepam tablets demonstrated compliance with pharmacopeia requirements for uniformity of mass, uniformity of content, and disintegration time. In vitro digestion-permeation studies revealed greater permeation across an artificial lipid membrane for the 3D-printed clonazepam tablets in comparison to a marketed product. Overall, the results demonstrated the possibility of 3D printing personalized and child-friendly oral dosage forms of high quality, using emulsion gel as a drug delivery system for poorly-water soluble drugs.