Page 52 - IJB-10-6

International Journal of Bioprinting Semi-solid extrusion for pediatric medicine

In view of these drawbacks, we consider that the material and numerical parameters. Machine parameters
FFF process is not currently the most suitable option for are the characteristics of the equipment used to print the
compounding in pediatric oncology hospitals. drug, such as the design and number of printheads or the
diameter of the nozzle.
2.2. Semi-solid extrusion
2.2.2. Dosage form design by computer-aided design
2.2.1. Process overview Operating parameters affect the quality attributes of the
The other extrusion-based AM process is SSE. Unlike finished product. The design of the dosage form mainly
FFF, SSE uses a semi-solid (or semi-molten) raw material, includes its geometry, dimensions, and infill density.
usually placed in a syringe or cartridge and extruded at low Design geometry is an editable parameter, where the
temperatures, generally between ambient temperature exchange surface can be adjusted to modify the API release
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and 80°C (Table 1). The material is extruded by applying kinetics. Different dosage form dimensions can alter the
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sufficient pressure in two main ways. The first approach quantity of API in the finished product (e.g., larger dosage
is pneumatic extrusion, whereby the piston of the forms contain more API). Additionally, the size of the
syringe containing the pharmaceutical ink is pushed by dosage form is strongly correlated with its mass. The
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compressed air pressure. The pressurized air is connected infill density of the dosage form can be varied to obtain
directly to the syringe body, whose nozzle can incorporate different properties and release profiles. Generally, porosity
a valve to control the air channel into the printhead via is retained to facilitate API release; thus, infill density rarely
an on-off switch, closing the channel when the valve is reaches 100%. By adjusting these parameters during drug
switched off (Figure 2). The advantages of this system production via SSE, it is possible to tailor the dosage form
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are high precision in material extrusion, fast response to meet the specific needs of the patient, ensuring precise
time as the syringe body can be instantly pressurized, control over the drug’s characteristics and performance.
and suitability for viscous materials (as the gas can reach
high pressures without compromising system integrity). 2.2.3. Pharma-ink and dosage forms
However, it is less effective for low-viscosity materials and The 3D printing material, also called the Pharma-ink (a
is more complex compared to mechanical systems. 80,81 The mixture of drugs and excipients), should possess several
second approach is mechanical extrusion, utilizing either ideal characteristics: it should be easy to prepare without
a piston or a screw controlled by stepper motors to push using heat, adhere minimally to facilitate packaging in
the material through the nozzle (Figure 3). Mechanical the 3D printer while ensuring sufficient adhesion of the
extrusion is more affordable and easier to transport semi-solid mass to the printing bed, be smooth and free
than the pneumatic system, as it does not require an of lumps, and be easily incorporated into a syringe. Finally,
air compressor. Furthermore, syringes can be replaced the dynamic viscosity of the ink must be sufficiently high,
quickly and easily, speeding up the printing process. with shear-thinning properties, to be printable without
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However, it is not suited for high-viscosity materials. collapsing once extruded. Table 1 provides a non-
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exhaustive literature review of articles published between
The quality of dosage forms manufactured by SSE is 2021 and 2024 on drugs manufactured via SSE. The most
influenced by three categories of parameters: material common dosage forms are solid oral forms, predominantly
parameters, operating parameters, and machine swallowable dosage forms (films or tablets). Other solid
parameters. These parameters interact with each other oral dosage forms produced by SSE include orodispersible
and influence the quality of the finished products, and chewable forms. One advantage of SSE over FFF is
including API content and uniformity, release kinetics, its ability to manufacture solid dosage forms with a soft
mass and mass uniformity of printed products, product texture, allowing for the creation of chewable printlets. For
appearance, and mechanical properties (e.g., surface example, gummies made by Rouaz-El Hajoui et al. contain
roughness, dimensional accuracy, hardness, etc.). gastro-resistant pellets with the API, enabling the
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Material parameters refer to the formulation, particularly modified release of the API while still allowing chewing of
the material’s rheological properties and, to a lesser the dosage form (Figure 4). While most of these solid oral
extent, its thermal properties. Operating parameters dosage forms are designed for systemic pharmacological
are those that can be modified during print production, action, there are a few examples intended for local action
i.e., numerical parameters and physical parameters. in the stomach, such as gastro-floating devices. Other
Numerical parameters enable modulation of the dosage notable forms include mucoadhesive films like vaginal
and kinetics of print release from the 3D model; ovules made by Teworte et al., rectal forms, such as
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physical parameters designate the selection of optimal infliximab suppositories made by Awad et al. (Figure 5),
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temperature, pressure, and print speed as a function of and medical devices impregnated with active substances,

Volume 10 Issue 6 (2024) 44 doi: 10.36922/ijb.4063