Page 47 - IJB-10-6

International Journal of Bioprinting Semi-solid extrusion for pediatric medicine

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 (e.g., drug formulations)
directly from digital models, allowing for high precision and customization. 3D-printed formulations have displayed
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, which is essential for managing conditions that require precise therapeutic control. The paper
discusses several case studies using the semi-solid extrusion (SSE) process for producing personalized dosage forms,
along with various technical and regulatory challenges associated with implementing this process in hospital-based
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.

Keywords: Unlicensed preparation; 3D printing; Pediatrics; Semi-solid extrusion; Hospital preparation;
Personalized medicines

1. Introduction generic status and are priced similarly to the original
drug. Between 2007 and 2016, 267 new medicines and
The lack of availability of appropriate medicines for children 43 new dosage forms for children’s use were authorized.
has been an extensive and well-known problem for many Unfortunately, despite these incentives, only seven PUMAs
years. Children require medicines that are adapted to each have been obtained since 2006. Pediatric medicines
1
12
age group, due to the remarkable heterogeneity of this remain underdeveloped, particularly in areas such as
population, which ranges from premature infants to young anticancer drugs, cardiology, or diseases affecting only
adults. Some medicines are not suitable for young children, children. 10,13–19 To achieve better results, Europe is in
and even less so for premature infants. Furthermore, the process of amending its incentive rules (Regulation
2–4
differences in the pharmacokinetic and pharmacodynamic 726/2004 and Directive 2001/83/EC) and the legislation
profiles of children and adults necessitate different dosage on medicines for children and rare diseases (Regulation
strengths for children. Moreover, the preferred dosage 1901/2006 and Regulation 141/2000/EC, respectively).
form for children evolves with age and must be adapted to
account for varying weights, forms, and taste preferences, Children are a particularly vulnerable patient group
which can differ from country to country. Consequently, with limited pharmaceutical treatment options. Drug
5
there is a strong demand for medicines that are suitable shortages have been associated with higher relapse rates
for children, easy to administer, use non-toxic excipients, in children with cancer, the use of less effective agents,
reduced dosage frequency, good palatability, and flexible off-label use, and a greater risk of both short- and long-
20
dosing. When developing a medicine, the choice of term toxicity. Drug shortages negatively impact patients
6,7
pediatric forms is most often made in favor of oral liquid by affecting drug therapy, causing delays in medical
forms, despite their limitations, including stability issues, procedures or therapy, and contributing to medication
difficulty in achieving controlled-release formulations, errors. 21,22 Therapeutic alternatives, where they exist, are
the need for multiple-day dosing, exposure to potentially often associated with higher cost, lower efficacy, increased
harmful excipients, poorer palatability, and higher costs. side effects, off-label use, and medication errors due to
From an industrial perspective, these constraints represent inexperience and lack of knowledge. 23,24
a significant challenge. 8–11 Despite efforts by health authorities to promote the
Numerous incentives from the United States (US) development of pediatric medicines, many medicinal
Food and Drug Administration (FDA) and the European products are authorized only for adults and are not currently
Medicines Agency (EMA), such as Pediatric Investigation available in formulations suitable for administration to the
Plans, are mobilized in order to develop new formulations pediatric population. As a consequence, off-label or even
adapted for children with specific indications, allowing unlicensed practices are frequent and their prevalence has
them to achieve Pediatric-Use Marketing Authorization been estimated to range from 3.2% to 95% overall, 26–95%
(PUMA) status. In contrast, pediatric formulations of in neonates, 25–27 2.7–51.2% in outpatients, and 9.0–79.0%
drugs already on the market typically receive only hybrid in inpatients. 28,29 Caregivers or parents often modify off-

Volume 10 Issue 6 (2024) 39 doi: 10.36922/ijb.4063