Biomimetic replenishment therapy of cortisol using semi-solid extrusion – 3D printed tablets for adrenal insufficiencies

Abstract

Adrenal insufficiency, an orphan disease, may lead to significant morbidity despite its rare occurrence. Therefore, it requires a daily replacement therapy of hydrocortisone, which displays a highly variable pharmacokinetic profile in individual patients, highlighting the need for personalized dosing. Like most hormones, cortisol follows a circadian rhythm and most conventional dosage forms fail to result in an accurate chronorelease profile. Semi-solid extrusion 3D printing can design unique dosage forms that have the potential to address such needs. Despite several developments and investigations in this area, the existing formulations either fail to facilitate the nocturnal release of cortisol or are unable to meet the personal requirements of patients. Our investigation, thus, focuses on a tablet-in-tablet (core–shell tablet) approach to enable nocturnal release of hydrocortisone and provide personalized dosing. The shell consisted of Klucel™ HF, which acted as rate limiting barrier and provided an initial delayed release of the drug whereas the core comprised of the drug, along with soluble and insoluble diluents, suspended in Klucel™ JF gel. The resulting paste was characterized by its rheology. The optimum parameters for printing both, the core and shell paste were found to be nozzle gauge of 21G, printing speed of 15 mm/s, and the layer height of 0.51 mm. Physicochemical characterization of tablets was conducted with respect to measuring their breaking force, friability, drug content, FTIR, X-ray powder diffraction, SEM, and in-vitro dissolution. This work successfully demonstrates the potential of SSE 3D printing to fabricate Chronotherpeutic release personalized tablets to improve patient compliance and treatment adherence.