Page 60 - IJB-10-6

International Journal of Bioprinting Semi-solid extrusion for pediatric medicine

requirements (e.g., API content, release kinetics, etc.). In general, pressure measurement can be used to establish
80
Rheological properties also influence the nozzle and print correlations between pressure and critical quality attributes
bed temperatures: higher viscosity typically requires higher of the finished product (e.g., mass, dimensions, etc.). 81
printing temperatures for extrusion. Compared to FFF,
SSE has two main advantages: the required temperatures 2.3. Post-processing steps
are lower, generally between ambient temperature and Post-processing is an optional stage in the 3D printing
80°C (Table 1); and the printing rate is generally faster. process. For SSE, when post-treatment is necessary, it is
81
For instance, Hu et al. reported that 50 dosage forms almost always drying (Table 2). Drying involves removing
can be printed in 13–15 min. To facilitate technology water or other volatile liquids from a product, either in a
113
transfer between teams, it is important to translate these free or adsorbed state. This step is often critical depending
80
rheological properties into force parameters for the on the quality attributes of the dosage form. The need
printer system. This data allows for the calibration of the for drying depends on material parameters, i.e., the
printers to obtain consistent results. 129,130 Additionally, it quantitative and qualitative composition of the pharma-
is crucial that the pharma-ink remains stable in terms of ink, as well as the thermal and rheological properties of
its rheological properties in the cartridge before printing, the material. It also depends on the printing temperature.
enabling on-demand printing without the need to prepare Drying influences the residual moisture content,
the pharma-ink each time. which affects various parameters of the product. For
2.2.5. Printheads and nozzle example, the limits of residual moisture content for
133
The nozzle diameter must be sufficiently precise to achieve orodispersible films are in the range of 3–6%. The
high resolution for the dosage form, ensuring accurate moisture content within orodispersible films influences
dosage and API release kinetics while minimizing the their chemical and microbiological stability, as well as
risk of obstruction due to the size of the raw material properties like stickiness, tensile strength, flexibility,
115
components or the rheological properties of the and disintegration time. Microbiological stability is a
material. 80,85 Consequently, the mean particle size of the particularly important parameter, given the transition
API should be smaller than a few hundred micrometers. 80 from a semi-solid gel containing a significant amount of
water to a solid oral dosage form, where the water activity
The number of print heads determines the range of must be reduced to less than 0.6 to minimize the risk of
printed products that can be produced by the machine. biological contamination. 111,134
Each nozzle can only handle one filament. Machines with
at least two nozzles are particularly advantageous for In the reviewed articles, three possibilities regarding
multi-layer printed products (also known as polypills). post-processing are noted: (i) obtaining a finished
These machines can alternate between layers containing product without post-processing 83,84,89,93,95,100,101,103,107,120,121 ;
two different APIs or between an API and an excipient. (ii) drying is necessary (Table 2); and (iii) other post-
There are several examples of polypills produced using treatment operations, besides drying, are necessary, such
SSE technology. 131,132 as crosslinking the printed parts, 104,123 adsorption of the
active substance or coating.
126
119
2.2.6. Extrusion pressure
Pressure is a critical parameter in the SSE process. The The most common drying method is open-air drying at
81
pressure applied to the top of the syringe containing room temperature, with drying times generally between 12
the raw material increases progressively until a certain and 48 h. Drying is also carried out in an oven (sometimes
threshold is reached, at which point the material begins to under vacuum), at low temperatures (20–80°C), for
be extruded. The extrusion rate is directly correlated with periods ranging from a few hours to 24 h. The printing
the pressure applied, making it essential for this pressure bed is sometimes used to dry printed materials, with
to remain constant with only slight fluctuations to ensure temperatures of 60–70°C for 10 min to 2 h. Desiccators
the quality of the finished product. Poorly controlled or freeze-drying are sometimes used. Some studies
81
pressure would lead to inconsistencies in material flow, combined different drying techniques. Falcone et al. used
potentially affecting API content. Therefore, pressure must a combination of open-air drying, a low-power microwave
be accurately measured using sensors integrated into the (200–400 W), an oven, and a desiccator. Except for freeze-
92
3D printer. These sensors can detect process problems, drying, most drying techniques are simple and do not
e.g., a clogged nozzle would be signaled by an unexpected require complex equipment, making them feasible to use
increase in pressure or the presence of air in the syringe that with SSE in hospitals. However, these methods generally
would be indicated by an unexpected drop in pressure. require several hours to complete.
81

Volume 10 Issue 6 (2024) 52 doi: 10.36922/ijb.4063