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Hospital 3D-printed cyclophosphamide printlets for paediatric patients
Malissa Boucida1, Stéphanie Ramos2, François-Xavier Legrand3
1Département de Pharmacie Clinique, Gustave Roussy, 94805 Villejuif, France.
Insights
3D printing created chewable cyclophosphamide (CPA) "printlets" for children, meeting World Health Organization targets for flexible dosing and stability. This innovation offers a personalized oral formulation for paediatric oncology.
Area of Science:
- Pharmaceutical Technology
- Drug Delivery Systems
- Paediatric Formulations
Background:
- Cyclophosphamide (CPA) is vital in paediatric oncology, but limited oral formulations hinder flexible dosing.
- The World Health Organization (WHO) has outlined a Target Product Profile (TPP) for paediatric CPA, emphasizing age-appropriate solid dosage forms.
Purpose of the Study:
- To develop and characterize a 3D-printed, chewable cyclophosphamide (CPA) formulation meeting WHO TPP and clinical needs.
- To create a flexible, dose-adapted oral formulation for paediatric cancer treatment.
Main Methods:
- Formulation of a 10% (w/w) CPA starch-polyol ink for semi-solid extrusion (SSE) 3D printing.
- Development of a discrete dose library (7-40 mg) based on prescription analysis.
- Systematic evaluation of printlet quality, dissolution, and stability (2-8°C, ambient).
Main Results:
- The 3D-printed dose library accommodated most prescribed CPA doses.
- All printlets met pharmacopeial standards, exhibiting rapid, immediate-release dissolution.
- Printlets demonstrated physicochemical stability for at least 6 months under refrigeration, with low water activity and crystalline drug content.
Conclusions:
- 3D printing enables personalized, hospital-based oral cyclophosphamide (CPA) formulations for paediatric patients.
- The developed formulation principles are applicable to other hydrolysis-sensitive cytotoxic drugs.
- This approach addresses the need for flexible, stable, and age-appropriate paediatric drug delivery.
Abstract:
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.
