Page 522 - IJB-9-6

International Journal of Bioprinting Advances for 3D-printed oral drug delivery systems

In 2021, Wang et al. employed the ASTREE In order to evaluate the structure–function relationship
electronic tongue to design the additives of binder of various fused deposition 3D-printed tablets, Zhang et al.
jetting 3D-printed levetiracetam instant dissolving used Box–Behnken design, with the experimental design
tablets [81] . Different formulations were created, and their based on the effect of design parameters and responses
palatability was examined using ASTREE and design of (drug loading, mechanical properties, and in vitro drug
experiment (DoE). The oral dispersion time and in vitro release performance) . Shell thickness, infill density, and
[84]
drug release were predicted with a texture analyzer layer height were chosen as the independent variables. The
and a dissolution apparatus. The results showed that results of this research revealed a favorable future of patient-
the electronic tongue had an excellent ability for taste focused drug production and on-demand manufacturing,
discrimination. The credibility of the results of the with inputs from experts (doctors, pharmacists,
electronic tongue was evaluated with human gustatory formulation scientists, and pharmaceutical engineers)
sensation tests [81] . throughout the fabrication process. Design of experiments
Using a toolbox of modern techniques, Desai et al. can contribute to robust guidance for formulation and
[84]
assessed 3D-printed orodispersible films in terms of optimization of 3D-printed dosage forms .
disintegration, taste, texture, and mouthfeel, as they affect The printability parameters of selective laser sintering
the sensory perception. Three in vitro methods were in 3D-printed solid dosage forms loaded with copovidone
applied: Petri dish (disintegration), oral cavity model and paracetamol were evaluated by Gueche et al. .
[85]
(disintegration), and bio-tribology (disintegration and oral The influence of the heating temperature was verified
perception). The findings suggested good oral palatability individually, while Box–Behnken design was applied
and mouthfeel with higher molecular weight (MW). The to identify the effects of laser power, scan speed, and
toolbox can be used during the design process to raise layer thickness in the printability. Printing yield, height,
the positive perception of orodispersible films when weight, hardness, disintegration time, and percentage of
consumed, improving overall treatment acceptability . drug release were established as the measured responses.
[82]
The significance of three process parameters was
3.3. Quality assurance determined with an analysis of variance (ANOVA). With
This category includes a total of 34 papers and focuses on a QbD approach, this study demonstrated that the process
the quality of 3D-printed dosage forms at different levels: parameters are critical for printability .
[85]
design, processing, and repeatability. The sub-categories
are “quality by design,” “control verification,” “protocols Wang et al. explored the factors affecting fabrication
and standardization,” and “influence factors.” of binder jetting 3D-printed dosage forms using a two-
level full factorial design . Disintegration time, tensile
[86]
3.3.1. Quality by design strength, friability, dimensions (diameter and height
Products that do not meet their specifications or fail during accuracies), residual water content, weight, and drug
performance increase compliance costs and workload loading were selected as the critical quality attributes based
and reduce efficiency. Quality should be controlled on the quality target product profile (QTPP). The authors
at all development stages. Quality by design (QbD) concluded that QbD is a systematic and effective approach
[86]
aims to ensure the quality of medicines in their design, for efficient product design .
development, and manufacturing, by applying statistical, In 2022, Crișan et al. implemented a QbD approach
analytical, and risk-management tools .
[83]
to guide the development of fused deposition modeling
Nukala et al. applied multifactorial design to optimize 3D-printed diclofenac tablets . Risk management
[87]
3D-printed egglets for solvent extraction and drug strategies, design space definition, and DoE were employed
release . The mechanical manipulation of the egglets to reveal the effects that tablet design, tablet size, and
[65]
was evaluated and optimized considering: household layer height had on drug release and on the API content.
equipment, milling, particle size distribution, solvent The design strategy and appropriate formulation lead
extraction, and drug release. For the response surface to rapid release of the active pharmaceutical ingredient.
design, drug loading, infill density, and dimensions were Consequently, the model was accurate and can be employed
defined as critical quality attributes (CQA), while time for for the optimization of selected parameters .
[87]
85% of cumulative drug release (D85) and percentage of
drug extracted using water in 5 min (%S) were defined as 3.3.2. Control verification
the dependent variables. The technique was validated with 3D-printed oral DDS are usually created in small batches
a good correlation between the optimized response model due to equipment limitations, as they are smaller than a
and the generated data . manufacturing plant. Nondestructive quality verification
[65]

Volume 9 Issue 6 (2023) 514 https://doi.org/10.36922/ijb.1119