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International Journal of Bioprinting Semi-solid extrusion for pediatric medicine

the need to place the raw material (in liquid form) in to produce controlled-release forms and increase the
large quantities in a tank and cure it with ultraviolet (UV) apparent solubility of APIs by promoting the formation
light precludes the use of photosensitive materials and of amorphous solid dispersions. 60,69 Additionally, HME
complicates product changeovers. This results in extensive can be used to produce solid thermoplastic filament
cleaning requirements and an increased risk of cross- suitable for FFF/FDM. In FFF/FDM, the filament is
contamination. For these reasons, this process is also not fed through a print head with a heated nozzle that
suitable for drug manufacturing in hospitals. melts the material and deposits it layer-by-layer on the

Material jetting is an AM process that involves manufacturing platform. 52,53,55 Among the AM processes
spraying a liquid onto a substrate in droplets, triggered discussed, FFF/FDM is one of the least costly and easiest
60,64,70–78
by either piezoelectric or thermal stimulation. This to operate, providing good precision and versatility,
process includes two main types: (i) continuous inkjet and remains the most frequently used AM process in
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printing (where ink flow is continuous) and (ii) drop-on- the market.
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demand (where ink is jetted on demand). Depending Fused filament fabrication/fused deposition modeling
on the technology used, the drops could either solidify (FFF/FDM) offers several significant advantages. First, it
spontaneously or with the aid of heat or UV light. uses solid filament that can be easily stored and handled
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Among the reported dosage forms, oral and buccal during production, making it easy to set up on hospital
films have demonstrated significant promise for this premises. The filament is consumed precisely by the 3D
technology. 67,68 In 2024, material jetting meets most of printer for parts manufacturing, minimizing waste and
our criteria except the second one. Inkjet 3D printers simplifying cleaning, which involves only the nozzle and
currently used in pharmaceutical research are still in build platform onto which the material is deposited. This
the early stages of development and are essentially helps manage the risk of cross-contamination. Moreover,
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derived from conventional desktop printers, which are HME has long been used in the pharmaceutical sector,
not yet suitable for clinical use. Therefore, despite its providing access to a wide range of biocompatible
potential, this process is also excluded for hospital and excipients for use in FFF. The process does not require light
pharmacy use. exposure, enabling the use of photosensitive materials and
eliminating the need for post-printing treatments.
2.1.3. Extrusion processes
Extrusion is a mechanical manufacturing process where However, this process has significant limitations. Firstly,
the material is forced through a small hole (the die) under filament manufacturing by HME can be challenging to
pressure, transforming it into a homogeneous, plastic, manage within hospitals due to the complexity of achieving
semi-solid mass, known as the extrudate (typically a homogeneous distribution of APIs, making it difficult to
filament). In AM based on extrusion processes, the raw achieve at the point of care. The API can be incorporated
material is passed through a nozzle orifice and selectively either with the excipients in the extruder or post-extrusion,
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deposited layer by layer. The raw material may be in which complicates the process. Additionally, HME
solid form or semi-solid form. All extrusion-based AM equipment is costly and bulky. FFF also has a low printing
processes follow the same successive operations : material speed, i.e., 2–5 min to manufacture a single tablet, or >1
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loading, liquefaction, pressure application to move the h for a single batch of 30 prints. It is difficult to improve
material through the nozzle, extrusion, and controlled this speed due to the constraints of filament flow, which
layer-by-layer deposition along a predefined path, followed requires a balance between low viscosity for extrusion and
by bonding the successive layers. The specifics of SSE are high viscosity for layer adhesion. 60,70,76 Another drawback
discussed in the next section. is the need for high temperatures to melt the thermoplastic
filament, typically ranging from 100 to 250°C, which
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In fused filament fabrication (FFF), also known
as fused deposition modeling (FDM), the material is makes it difficult to manufacture drugs containing
heat-sensitive APIs.
a solid thermoplastic filament obtained through hot
melt extrusion (HME). HME uses a heat input to melt In terms of feasible dosage forms suitable for children or
thermoplastic materials, which may initially be in various the elderly, the FFF process is well-suited for manufacturing
forms, such as powders, granules, flakes, pastes, etc. The solid dosage forms for swallowing, including chewable
extrudate is produced continuously, and the size and forms, such as the mini-tablets developed by Parulski et
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shape of its cross-section are defined by those of the die. al. However, formulations produced using this process
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Established in the pharmaceutical industry in the 1980s, often result in dosage forms with high hardness and
HME is used to produce a variety of dosage forms (e.g., melting temperatures higher than 100°C, which makes
pellets, granules, implants, etc.). HME can also be used them unsuitable for suppositories or orodispersible forms.
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Volume 10 Issue 6 (2024) 43 doi: 10.36922/ijb.4063