ESPE Abstracts

Introduction: The current standard of care (SOC) for adrenal insufficiency (AI) is suboptimal due to fluctuating cortisol plasma concentrations. The sub- and supraphysiological cortisol levels, combined with the multi-day tablet intake, are associated with negative health outcomes and a poor quality of life. Furthermore, there is a high interindividual difference in the cortisol need, demanding a personalized approach. Pharmaceutical 3D printing (3DP) allows for adaptation of the drug dose, release profile, shape and taste, based on the individual patients’ need. The aim was therefore to develop 3D printed, personalizable hydrocortisone tablets for patients with AI. The secondary aims were (1) to compare the quality of 3D hydrocortisone with pharmacy compounded capsules, and (2) to assess the costs of manufacturing one 3D hydrocortisone tablet.

Methods: 10 mg hydrocortisone tablets were printed using semi-solid extrusion (SSE) and fused deposition modeling (FDM) 3DP. Pharmacy compounded 10 mg hydrocortisone capsules were purchased and analyzed, as comparator. Hydrocortisone content and drug release profiles were determined for each formulation. Different tablet volumes were printed to assess the correlation of tablet volume and hydrocortisone dose. Furthermore, a micro-costing study was performed to evaluate the manufacturing costs of 3D hydrocortisone.

Results: Direct release (DR) and sustained release (SR) tablets were successfully printed. Drug content of 3D tablets were closer to 10 mg compared to capsules. 3D tablets contained 103±5% and 98±1% hydrocortisone respectively for SSE and FDM, while capsules contained 92±1% - 94±1%. The drug dosage of 3D tablets was correlated (R²=0.999) to the predesigned volume of the tablets, providing a tool for dose personalization. The smallest tablets printed, had a diameter and height of 4 mm and 0.7 mm respectively. Manufacturing costs of 3D hydrocortisone was €1.90 - €3.20 per tablet, while costs of Plenadren or Efmody are far higher.

Conclusion: 3D printed SR and DR hydrocortisone tablets were developed for patients with AI. The quality of 3D tablets is higher than pharmacy compounded capsules, while manufacturing costs are feasible. The 3D therapy is once-daily, compared to three times a day of the SOC, reducing pill-frequency. Any desired dose can be printed, unlike the Plenadren®, making it easier to provide body-weight based dosing in pediatrics. Volume based dose personalization means the lower the dose, the smaller the tablet, leading to better palatability in pediatrics. Finally, the SR formulation needs optimization, to release for 24 hours. After optimization and validation, both 3D treatments will be assessed in-vivo.