Development and bioequivalence of 3D-printed medication at the point-of-care: bridging the gap towards personalized medicine.

Personalized medicine is currently hampered by the lack of flexible drug formulations. Especially for pediatric patients, manual compounding of personalized drug formulations by pharmacists is required. 3D printing of medicines, which enables small-scale manufacturing at the point-of-care, can fulfil this unmet clinical need. This study investigates the feasibility of developing a 3D-printed tablet formulation at the point-of-care which complies to quality requirements for clinical practice, including bioequivalence. Development, manufacturing and quality control of the 3D-printed tablets was performed at the manufacturing facility and laboratory of the department of Clinical Pharmacy and Toxicology at Leiden University Medical Center. Sildenafil was used as a model drug for the tablet formulation. With the 3D-printed tablets a randomized, open-label, 2-period, crossover, single-dose clinical trial to assess bioequivalence was performed in healthy adults. Bioequivalence was established if AUC 0-t and C max ratios were within the limits of 80.00 - 125.00%. The manufacturing process provided reproducible 3D-printed tablets that adhered to quality control requirements and were consequently used in the clinical trial. The clinical trial was conducted in twelve healthy volunteers. The 90% confidence intervals (CI) of both AUC 0-t and C max ratios were within bioequivalence limits (AUC 0-t 90% CI 87.28 - 104.14; C max 90% CI 80.23 - 109.58). For the first time we demonstrate the development of a 3D-printed tablet formulation at the point-of-care that is bioequivalent to its marketed originator. 3D printing of personalized formulations is a disruptive technology for compounding, bridging the gap towards personalized medicine.