3D printed personalized therapies for pediatric patients affected by adrenal insufficiency

Background

Adrenal insufficiency is usually diagnosed in children who will need lifelong hydrocortisone therapy. However, medicines for pediatrics, in terms of dosage and acceptability, are currently unavailable.

Research design and methods

Semi-solid extrusion (SSE) 3D printing (3DP) was utilized for manufacturing of personalized and chewable hydrocortisone formulations (printlets) for an upcoming clinical study in children at Vall d’Hebron University Hospital in Barcelona, Spain. The 3DP process was validated using a specific software for dynamic dose modulation.

Results

The printlets contained doses ranging from 1 to 6 mg hydrocortisone in three different flavor and color combinations to aid adherence among the pediatric patients. The pharma-ink (mixture of drugs and excipients) was assessed for its rheological behavior to ensure reproducibility of printlets through repeated printing cycles. The printlets showed immediate hydrocortisone release and were stable for 1 month of storage, adequate for prescribing instructions during the clinical trial.

Conclusions

The results confirm the suitability and safety of the developed printlets for use in the clinical trial. The required technical information from The Spanish Medicines Agency for this clinical trial application was compiled to serve as guidelines for healthcare professionals seeking to apply for and conduct clinical trials on 3DP oral dosage forms.

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Materials

High methyl-esterified (HM) pectin was obtained from Ceamsa (degree of esterification = 59.50%; pH = 3.20; O Porriño, Spain). Maltodextrin and maltitol were obtained from Roquette (Lestrem, France). Citric acid monohydrate, potassium citrate, yellow, green, and red colorants were purchased from Guinama (Valencia, Spain). Hydrocortisone base (MW 362.46 g/mol), strawberry, banana, and orange flavors were purchased from Acofarma (Barcelona, Spain). Methanol (HPLC grade) and potassium sodium tartrate tetrahydrate were obtained from Merck KGaA (Darmstadt, Germany), and formic acid (99–100% v/v) from VWR International (Radnor, USA). Hydrochloric acid (37%, Ph. Eur) was purchased from Scharlau (Barcelona, Spain), potassium dihydrogen phosphate from ITW Reagents (Barcelona, Spain), and sodium phosphate tribasic dodecahydrate (≥98.0% w/w) from Honeywell Fluka (Buchs, Switzerland). All materials were used as received.

Lucía Rodríguez-Pombo, Concepción Gallego-Fernández, Anna Kirstine Jørgensen, Carlos Javier Parramon-Teixidó, Carme Cañete-Ramirez, Maria Josep Cabañas-Poy, Abdul W. Basit, Carmen Alvarez-Lorenzo & Alvaro Goyanes, 3D printed personalized therapies for pediatric patients affected by adrenal insufficiency, Received 04 Jun 2024, Accepted 23 Aug 2024, Published online: 18 Sep 2024, https://doi.org/10.1080/17425247.2024.2399706

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