PhD defence N. (Nahman) Ayyoubi

Below is a brief summary of the dissertation:

There is a lack of suitable hydrocortisone formulations for patients with primary adrenal insufficiency. It is a rare disease, also known as Addison’s Disease, with a prevalence of 1-2 patients per 10,000 people. The current three times daily treatment with hydrocortisone does not mimic the physiological circadian plasma cortisol in patients. This leads to an increased risk of developing co-morbidities and mortality. The degree of cortisol deficiency is subject to interindividual variation related to differences in genetic and environmental influences. There is therefore a need for a hydrocortisone formulation that better mimics the gradual physiological cortisol plasma-concentrations, with the ability of flexible dose adjustment. We hypothesize in this thesis that using pharmaceutical 3D printing, a sustained release hydrocortisone formulation can be developed which mimics the physiological situation better. We tested this hypothesis by studying different 3D printing techniques, the quality of printed tablets and the cost of manufacturing. In this thesis, we have developed immediate and sustained release hydrocortisone formulations that better mimic physiological cortisol, while allowing flexible dose personalization using pharmaceutical 3D printing. The formulations comply to pharmacopeial quality standards and can be manufactured against acceptable costs. The quality of 3D printed products were higher compared to conventional pharmacy compounding methods. Our data support the use of pharmaceutical 3D printing as a safe and cost-effective method to manufacture personalized medicine. Moreover, it allows for the modification of drug release profiles, which is not possible using conventional pharmacy compounding techniques.