Endocrine 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. 3D printing (3DP) has gained momentum within the pharmaceutical field, moving from conceptual products, to clinical trials. This technology makes it possible to adapt the drug dose, release profile, shape and taste, based on the individual patients’ need. The aim was therefore to develop a 3D printed, personalized, sustained release (SR) hydrocortisone for patients with AI. Secondary aims were (1) to compare the quality of 3D medication to magistral capsules, which is the current standard of personalizing cortisol dose, and (2) to evaluate the manufacturing costs of 3DP.

Methods: 10 mg hydrocortisone tablets were printed using semi-solid extrusion (SSE) and fused deposition modeling (FDM) 3DP. 5 mg Plenadren®, slow-release tablets, and manually filled 10 mg hydrocortisone capsules were purchased and analyzed, as comparators. Hydrocortisone content (n=3–10), weights of final products and drug release profiles (n=3–6) were determined for each formulation. A micro-costing study was performed to evaluate the manufacturing costs of FDM 3D hydrocortisone in an academic hospital pharmacy setting.

Results: The 3D tablets had a stable release profile, similar to the Plenadren, where >80% of hydrocortisone was released in 24 h. Drug content of 3D printed tablets were closer to 10 mg compared to the purchased capsules. 3D printed tablets contained 103±5% and 98±1% hydrocortisone respectively for SSE and FDM, while capsules contained 92±1% – 94.5±0.5%. Manufacturing costs of 3D hydrocortisone was €1.90–€3.20 per tablet, compared to a purchasing price of €9.00 per capsule.

Conclusion: A 3D printed SR, personalized hydrocortisone formulation was developed for patients with AI. The quality of 3D tablets is higher than the capsules, while the manufacturing costs seem lower compared to the purchase price of capsules. Therefore, 3DP should replace manually filling of capsules in AI. The 3D therapy is once-daily, compared to three times a day of the SOC, reducing pill-burden. Any desired dose can be printed, unlike the Plenadren®. The 3D printed formulation will be tested in a clinical setting. A personalized delayed release 3D product is under development for the morning cortisol need in AI.