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- Katsiotis, Christos S., et al.
(author)
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Combinatorial 3D printed dosage forms for a two-step and controlled drug release
- 2023
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In: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 187
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Journal article (peer-reviewed)abstract
- Fused deposition modeling (FDM) and selective laser sintering (SLS) are two of the most employed additive manufacturing (AM) techniques within the pharmaceutical research field. Despite the numerous advantages of different AM methods, their respective drawbacks have yet to be fully addressed, and therefore combinatorial systems are starting to emerge. In the present study, hybrid systems comprising SLS inserts and a two-compartment FDM shell are developed to achieve controlled release of the model drug theophylline. Via the use of SLS a partial amorphization of the drug is demonstrated, which can be advantageous in the case of poorly soluble drugs, and it is shown that sintering parameters can regulate the dosage and release kinetics of the drug from the inserts. Furthermore, via different combinations of inserts within the FDM-printed shell, various drug release patterns, such as a two-step or prolonged release, can be achieved. The study serves as a proof of concept, highlighting the advantages of combining two AM techniques, both to overcome their respective shortcomings and to develop modular and highly tunable drug delivery devices.
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- Katsiotis, Christos S., et al.
(author)
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Processability of mesoporous materials in fused deposition modeling for drug delivery of a model thermolabile drug
- 2023
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In: International Journal of Pharmaceutics. - : Elsevier. - 2590-1567. ; 5
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Journal article (peer-reviewed)abstract
- The incorporation of drug-loaded mesoporous materials in dosage forms prepared with fused deposition modeling (FDM) has shown the potential to solve challenges relating to additive manufacturing techniques, such as the stability of poorly-soluble drugs in the amorphous state. However, the addition of these non-melting mesoporous materials significantly affects the mechanical properties of the filament used in FDM, which in turn affects the printability of the feedstock material. Therefore, in this study a full-factorial experimental design was utilized to investigate different processing parameters of the hot melt extrusion process, their effect on various mechanical properties and the potential correlation with the filaments' printability. The thermolabile, poorly-soluble drug ibuprofen was utilized as a model drug to assess the potential of two mesoporous materials, Mesoporous Magnesium Carbonate (MMC) and a silica-based material (MCM-41), to thermally protect the loaded drug. Factorial and principal components analysis displayed a correlation between non-printable MCM-41 filaments and their mechanical properties where printable filaments had a maximum stress >7.5 MPa and a Young's modulus >83 MPa. For MMC samples there was no clear correlation, which was in large part attributed to the filaments' inconsistencies and imperfections. Finally, both mesoporous materials displayed a thermal protective feature, as the decomposition due to the thermal degradation of a significant portion of the thermolabile drug was shifted to higher temperatures post-loading. This highlights the potential capability of such a system to be implemented for thermosensitive drugs in FDM applications.
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