The future of 3D printing for personalized medicine: Could 3D printed waffle shapes replace the magistral preparation of hydrocortisone capsules?

INTRODUCTION
Hydrocortisone (HCT) is mainly used in the substitution treatment of adrenal insufficiency (AS) which results in a disruption of the production of cortisol. The magistral preparation of HCT capsules in community pharmacies remains the only oral treatment adapted to the paediatric population due to the low doses administered. However, these preparations show non-compliance in mass and content uniformity. Three-dimensional (3D) printing appears as a potential solution because of the possibility to practise personalized medicine. The goal of this work is therefore to develop low-dose solid oral forms, of advanced pharmaceutical quality, containing HCT by HME and Fused Deposition Modeling (FDM) for the treatment of children against AS.

MATERIALS AND METHODS
The formulation contained HCT, Affinisol® 15LV (hydroxypropylmethylcellulose), Kollidon® VA 64 (vinylpyrrolidone-vinyl acetate), tri(ethyl)citrate and red iron oxide. HME was performed at 140°C and 50 rpm. Waffle shapes with diameters of 4.5, 6.0, 7.25 mm, heights of 2.0, 2.8 and 3.2 mm and drug loads of 2, 5 and 8 mg were printed at 155°C (Figure 1). The monograph uncoated tablets in European Pharmacopoeia 11th edition was used to characterize the printed forms. Dissolution studies were performed in 500 mL of HCl 0.1 M during 2 h. The HCT content was evaluated by a validated HPLC method. Friability test was performed at 25 rpm for 4 min.

RESULTS AND DISCUSSION
More than 80% of HCT was released in 45 min from waffle shapes containing 2, 5 and 8 mg of HCT, indicating a conventional drug release. The content uniformity of all 3D printed waffle shapes has shown encouraging results with maximum acceptance values lower than the requested value of 15.0. The differences in total weight before and after the test were lower than 1.0% for all 3D printed waffle shapes, which complied with the specifications.

CONCLUSION
Red 3D printed waffle shapes containing low-dose HCT for pediatric use were successfully developed by HME coupled to FDM. Content uniformity, drug dissolution and friability complied with the specifications, despite the considerable challenge of their small dimensions. 3D-printed solid oral forms could offer patients a higher pharmaceutical quality than capsules containing low-dose corticosteroids. Solid oral forms containing different dosages of API can be printed with the same filament, offering the prospect of practicing personalized medicine.