Breast cancer is the most frequently diagnosed cancer in women worldwide, and non-adherence to adjuvant hormonotherapy can negatively impact cancer recurrence and relapse. Non-adherence is associated with side effects of hormonotherapy. Pharmacological strategies to mitigate the side effects include coadministration of antidepressants, however patients remain non-adherent. The aim of this work was to develop medicines containing both hormonotherapy, tamoxifen (20 mg), along with anti-depressants, either venlafaxine (37.5 or 75 mg) or duloxetine (30 or 60 mg), to assess the acceptability and efficacy of this personalised approach for mitigating tamoxifen side effects in a clinical trial. A major criterion for the developed medicines was the production rate, specified at minimum 200 dosage units per hour to produce more than 40,000 units required for the clinical trial. A novel capsule filling approach enabled by the pharmaceutical 3D printer M3DIMAKER 2 was developed for this purpose. Firstly, semi-solid extrusion 3D printing enabled the filling of tamoxifen pharma-ink prepared according to French compounding regulation, followed by filling of commercial venlafaxine or duloxetine pellets enabled by the development of an innovative pellet dispensing printhead. The medicines were successfully developed and produced in the clinical pharmacy department of the cancer hospital Gustave Roussy, located in Paris, France. The developed medicines satisfied quality and production rate requirements and were stable for storage up to one year to cover the duration of the trial. This work demonstrates the feasibility of developing and producing combined tamoxifen medicines in a hospital setting through a pharmaceutical 3D printer to enable a clinical trial with a high medicines production rate requirement.

Adherence to treatment is one of the major challenges in chronic diseases. Inappropriate dosage forms or bad taste are the main factor for non-adherence, especially in paediatric patients. 3D printed medicines could be tailored to specific patients to make medicines more acceptable, however the clinical implementation in hospitals is still limited. This study addresses the challenge of developing pharma-inks (mixtures of drugs and excipients) for semi-solid extrusion (SSE) to produce chewable tablets of Sulfamethoxazole (SMX) and Trimethoprim (TMP) for paediatric oncology patients in a hospital setting. SMX and TMP pharma-inks were stable and printable on demand for more than 3 months. The chewable tablets were also stable, and the drugs dissolution profiles were comparable to those of the commercial formulations, indicating potential bioequivalence. Human sensory evaluations confirmed that the formulation improved palatability compared to traditional suspensions. 3D-printed SMX/TMP formulations are an alternative to traditional formulations for paediatric patients in hospital settings, enhancing acceptability and adherence while enabling personalized dosing.

The long-standing issue of inadequate medicine formulations has been a focus of regulatory bodies and pharmaceutical research, particularly in adapting medicines for children’s unique requirements. The pediatric population presents diverse challenges in pharmacotherapy due to their varying age-related physiological differences, taste and dosage form preferences. Conventional formulations often fail to meet these needs, leading to high prevalence of off-label medication use and modifications by caregivers, which can compromise drug efficacy and safety. The well-known problems of managing children's medication are very similar to those encountered in geriatrics, which also require doses to be adapted to the patient's pathophysiological characteristics to avoid deglutination problems. This paper explores recent innovations in drug formulations, highlighting the shift from traditional liquid formulations to solid dosages through 3D printing technology. Recent advancements in 3D printing technology offer promising solutions to these challenges. Additive manufacturing (AM), or 3D printing, facilitates the creation of complex objects including drug formulations, directly from digital models, allowing for high precision and customization. 3D printed formulations have shown considerable promise in improving palatability, adherence, and dose accuracy for pediatric use. Innovations like chewable tablets and taste-masked formulations make medications more acceptable to children. Moreover, the ability of 3D printing to adjust drug release profiles and doses offers a personalized approach to pediatric and geriatric pharmacotherapy, essential for conditions requiring tight therapeutic control. The paper discusses several case studies based on the semi-solid extrusion (SSE) process that enables the production of personalized dosage forms and the various technical and regulatory challenges to implementing this process in hospitals for drug manufacturing. In conclusion, while 3D printing in pediatric and geriatric pharmacotherapy addresses many challenges of traditional drug formulations, ongoing research and adaptation of regulatory frameworks are necessary to expand its application, ensuring safer, more effective, and more acceptable medication.

The development of oral pediatric forms by pharmaceutical companies is still insufficient. In fact, many drugs used in paediatric oncology, such as temozolomide, are not labeled and adapted for paediatric use. Temozolomide (TMZ) is an alkylating agent used as the standard of care for many adult and pediatric brain tumours, such as neuroblastoma, glioblastoma and medulloblastoma. The present study was carried out to propose a suitable and palatable formulation of the oral liquid preparation of TMZ. The suspension is composed of TMZ suspended in SyrSpend SF pH 4, as well as TMZ crystallization stabilizing agents and sweetening agents. To reach this formulation, several taste-masking agents were evaluated. Here, we describe the method of preparation of the formation as well as the monocentric population treated with the formulation over a 5–year period. A 20 mg/mL TMZ suspension was developed. TMZ suspension is stable for 6 weeks, stored between 2 and 8 degrees, protected from light, and compatible with nasogastric tubes. Thirty-eight patients participated in the palatability study and choose cola flavour, and 104 patients were treated in Gustave Roussy with the developed suspension; no unexpected event was reported. To conclude, we propose here a new TMZ liquid formulation which is stable for at least 6 weeks and well-tolerated with extensive feedback.