Background Optimal cortisol replacement therapy for patients with adrenal insufficiency (adr-ins)  should mimic the cortisol diurnal rhythm. The standard of care is suboptimal due to  fluctuating plasma cortisol concentrations caused by immediate release tablets. These fluctuations are associated with negative health outcomes. Furthermore, there is a high inter-individual difference in the cortisol need per patient, while there is a lack of individualized hydrocortisone (HC) on the market. There is thus an unmet need for a sustained release (SR), once-daily, personalized hydrocortisone tablet for patients with adr-ins. The aim of this study  was to assess whether patient-tailored SR hydrocortisone tablets can be produced using 3D printing (3DP). The added benefit of 3DP is that any desired dose can be printed which enables dose personalization.
Methods 10 mg HC tablets were printed using semi-solid extrusion (SSE) 3DP. One batch was printed using fused deposition modeling (FDM) 3DP, 5 mg Plenadren® tablets and pharmacy compounded 10 mg HC capsules were purchased and analyzed, for comparison purposes. HC content (n=10), weights of final products and release profiles (n=6) were determined for each formulation.
Results SSE tablets had a stable release profile, similar to the Plenadren, where >80% of content was released in 24h. Furthermore, the weights of the SSE batches had an RSD<4%, complying to compounding guidelines. Drug content of the 3D tablets were closer to 10 mg compared to capsules. 3D printed tablets contained 103±5% and 98±1% respectively for SSE and FDM, while the capsules contained 92±1%.
Conclusion A 3D SR, personalized hydrocortisone formulation was developed for patients with adr-ins. Personalized cortisol therapy should be produced with 3DP rather than compounding capsules to prevent undertreatment.  The quality of 3D printed tablets is higher compared to the capsules. Therefore, 3D printing should completely replace manually filling of capsules in cortisol replacement therapy. The 3D printed formulation will be tested in a clinical setting.