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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.

Fused deposition modelling (FDM) is the most extensively employed 3D-printing technique used in pharmaceutical applications, and offers fast and facile formulation development of personalized dosage forms. In the present study, mesoporous materials were incorporated into a thermoplastic filament produced via hot-melt extrusion and used to produce oral dosage forms via FDM. Mesoporous materials are known to be highly effective for the amorphization and stabilization of poorly soluble drugs, and were therefore studied in order to determine their ability to enhance the drug-release properties in 3D-printed tablets. Celecoxib was selected as the model poorly soluble drug, and was loaded into mesoporous silica (MCM-41) or mesoporous magnesium carbonate. In vitro drug release tests showed that the printed tablets produced up to 3.6 and 1.5 times higher drug concentrations, and up to 4.4 and 1.9 times higher release percentages, compared to the crystalline drug or the corresponding plain drug-loaded mesoporous materials, respectively. This novel approach utilizing drug-loaded mesoporous materials in a printed tablet via FDM shows great promise in achieving personalized oral dosage forms for poorly soluble drugs.

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.

Poorly soluble drugs represent a substantial portion of emerging drug candidates, posing significant challenges for pharmaceutical formulators. One promising method to enhance the drug’s dissolution rate and, consequently, bioavailability involves transforming them into an amorphous state within mesoporous materials. These materials can then be seamlessly integrated into personalized drug formulations using Additive Manufacturing (AM) techniques, most commonly via Fused Deposition Modeling. Another innovative approach within the realm of AM for mesoporous material-based formulations is semi-solid extrusion (SSE). This study showcases the feasibility of a straightforward yet groundbreaking hybrid 3D printing system employing SSE to incorporate drug-loaded mesoporous magnesium carbonate (MMC) into two different drug formulations, each designed for distinct administration routes. MMC was loaded with the poorly water-soluble drug ibuprofen via a solvent evaporation method and mixed with PEG 400 as a binder and lubricant, facilitating subsequent SSE. The formulation is non-aqueous, unlike most pastes which are used for SSE, and thus is beneficial for the incorporation of poorly water-soluble drugs. The 3D printing process yielded tablets for oral administration and suppositories for rectal administration, which were then analyzed for their dissolution behavior in biorelevant media. These investigations revealed enhancements in the dissolution kinetics of the amorphous drug-loaded MMC formulations. Furthermore, an impressive drug loading of 15.3 % w/w of the total formulation was achieved, marking the highest reported loading for SSE formulations incorporating mesoporous materials to stabilize drugs in their amorphous state by a wide margin. This simple formulation containing PEG 400 also showed advantages over other aqueous formulations for SSE in that the formulations did not exhibit weight loss or changes in size or form during the curing process post-printing. These results underscore the substantial potential of this innovative hybrid 3D printing system for the development of drug dosage forms, particularly for improving the release profile of poorly water-soluble drugs.