Hospital 3D-printed cyclophosphamide printlets for paediatric patients

Cyclophosphamide (CPA) remains a cornerstone of paediatric oncology, including in metronomic regimens, but its oral formulations are limited, necessitating the development of dose-adapted formulations. Recently, the World Health Organization (WHO) defined a Target Product Profile (TPP) advocating age-appropriate solid oral dosage forms with flexible dosing and multi-month stability for paediatric cyclophosphamide. Here, the development and characterisation of a 3D-printed chewable cyclophosphamide "printlet" designed to meet this TPP and local prescribing practices are reported. Retrospective analysis of hospital prescriptions informed the design of a discrete dose library ranging from 7 to 40 mg. A single 10% (w/w) CPA starch-polyol ink was formulated for semi-solid extrusion (SSE) 3D printing. The printlets were systematically evaluated for water activity, solid-state properties, mass and content uniformity, dissolution behaviour, and physicochemical stability under refrigerated and ambient conditions. The dose library covered most clinically prescribed doses, while all tested units met pharmacopeial quality requirements and exhibited rapid, immediate-release dissolution. Low water activity and a predominantly crystalline drug state supported stability for at least 6 months under refrigerated conditions (2-8 °C), with no significant loss of cyclophosphamide content. This work demonstrates the feasibility of a hospital-based, personalised 3D-printed oral CPA and provides formulation principles applicable to other hydrolysis-sensitive cytotoxic drugs.