Page 48 - IJB-10-6

International Journal of Bioprinting Semi-solid extrusion for pediatric medicine

label medicines before administration, such as crushing for medication management, particularly as polypharmacy
tablets into powder, opening capsules and diluting is so common. Therefore, geriatric patients require
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the powder in a liquid, or drinking injectable drugs. personalized treatment using compounded medicines, just
However, such modifications can have potentially harmful as pediatric patients do. 45
consequences for a pediatric patient. These practices may Overall, the use of unlicensed preparations has increased
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affect the efficacy and safety parameters of the medicinal over the last 10 years, especially as they are also used to
product by altering its absorption characteristics, stability, compensate for drug shortages, such as anesthetic drugs
and palatability. 31–33 Such manipulation presents a risk during the COVID-19 crisis or amoxicillin since 2022. 46
of medication errors in dose calculation or preparation,
leading to inaccurate dosing and undetermined effects on Furthermore, unlicensed preparations can be tailored to
the product’s stability. 30,34 Additionally, crushing tablets or individual patients or produced at a larger semi-industrial
opening capsules exposes caregivers or family members scale. Since compounding carries the risk of contamination
to chemical risks associated with the active substance, and supra- and subtherapeutic errors, it demands highly
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particularly when it is carcinogenic. trained personnel and premises that are no longer available
Due to the lack of appropriate medicines for children, in all pharmacies in many countries. To ensure the quality
compounded medicines (i.e., unlicensed preparation) of the preparations and their safe use, regulations must be
can play an important role in addressing needs unmet adapted to these different production scales. For example,
by commercial medicines or during drug shortage. 35,36 the FDA has revised its recommendations to provide more
Unlicensed preparations are produced by the community flexibility to hospital pharmacies and health systems in the
and hospital pharmacies, offering capsules or oral liquid distribution of compounded drugs, while emphasizing the
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formulations adapted to patients’ needs. The need for importance of ensuring their safety and efficacy. In France,
adapted treatment through compounding is significant, new regulations allow for the production of medium-sized
especially in conditions with narrow therapeutic margins, batches, with a corresponding increase in quality towards
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long-term treatments, and medications where non-adapted Good Manufacturing Practice (GMP) standards. In
dosages or non-compliance can jeopardize patient survival, this context, 3D printing emerges as a valuable tool for
such as cancer, autoimmune diseases, and cardiology. 10,34 creating custom shapes and doses, enhancing the quality
For example, a recent study on hospital preparations in of pediatric preparations. 42
oncology by the European Society for Paediatric Oncology Since the 2010s, there has been increasing enthusiasm
(SIOPE) and the European Society of Oncology Pharmacy among academic, hospital, and community pharmacies, as
(ESOP) identified 28 formulations for 13 different active well as the industry, for additive manufacturing (AM) of
pharmaceutical ingredients (APIs) used in chemotherapy drugs. 50,51 Better known as 3D printing, AM is a process
and 35 formulations for 16 different APIs used in supportive of creating a physical object by joining materials layer by
therapy, each with a sufficient level of evidence. In some layer from a digital 3D model. All AM processes can be
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cases, more sophisticated formulation strategies, such as divided into a sequence of operations integrated within
encapsulation of drug particles or 3D medicine printing, a digital chain, which comprises four distinct stages. 53–55
are highly promising and have demonstrated a significant The first stage is computer-aided design (CAD), which
benefit over traditional extemporaneous preparation. involves creating a 3D digital model and converting its
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Such robust and adaptive techniques could facilitate surfaces into a network of polygons, typically triangular
access to personalized therapy for all pediatric patients. 38,39 facets. The positions of these facets are then translated
Scientific publications and recent industry strategies into instructions for the 3D printer, written in G-code.
indicate a clear shift from liquid dosage forms to novel solid The second stage is the preparation of the digital model
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dosage forms. This new technology improves palatability, prior to manufacturing, which involves optimizing and
provides flexibility in the design of child-friendly dosage repairing the digital model before slicing it into layers.
forms, and could enable cost-effective, individualized The third stage is computer-aided manufacturing (CAM),
treatment options. However, further research in this field which involves manufacturing the physical object layer
is evident. 41–43 by layer. The fourth stage is post-processing, which is
The common challenges of managing children’s optional depending on the objects manufactured and the
medication are similar to those encountered in geriatrics. technology used. This stage consists of a series of steps
Similarly, geriatric patients require dose adjustments carried out after the completion of a manufacturing cycle
according to their physiological characteristics and galenic to ensure the finished product has the desired properties
compounding to compensate for deglutination problems. (e.g., support removal, drying, coating, polishing, coloring,
Swallowing difficulties in older adults present challenges smoothing, etc.).

Volume 10 Issue 6 (2024) 40 doi: 10.36922/ijb.4063