3D printed hydroxyurea for pediatric use: toward personalized formulations and reduced exposure risk

Sickle cell anemia is one of the most frequent severe monogenic disorders in the world, with the highest prevalence in Sub-Saharan Africa, India, the Middle East, and in populations with ancestry from these regions. Currently, hydroxyurea is recommended as a primary prevention from 9 to 12 months of age in infants affected by this condition, with doses adjusted upon weight and biological parameters. Because treatment is initiated early and maintained throughout life, the lack of age-adapted, palatable formulations poses major challenges to long-term adherence. To address this issue in children able to chew solid dosage forms, we developed a customizable, pediatric-friendly 3D printed hydroxyurea formulation. Hydroxyurea was incorporated at 30 % weight/weight into a pectin-based chewable "pharma-ink" and successfully printed into gummy-like chewable tablets containing 200-600 mg hydroxyurea using a semi-solid extrusion 3D printer. The resulting printlets were comprehensively characterized according to the United States Pharmacopeia recommendations. They demonstrated nearly 100 % drug loading with no detectable degradation, ensuring accurate dose delivery. In vitro release testing confirmed compliance with the United States Pharmacopeia specifications for immediate-release hydroxyurea. In vivo pharmacokinetic profiles in Beagle dogs were comparable to those of conventional hydroxyurea suspensions. A 90-day stability study under ambient conditions revealed no degradation or change in hydroxyurea release. Although occupational exposure was not directly quantified, the workflow design plausibly reduces preparation risks compared with current compounding practices, an aspect that will be addressed in future clinical studies.