Additive manufacturing (AM) has turned a new leaf in manufacturing related to numerous disciplines, including healthcare industries. The rapid layer-by-layer prototyping of the designed 3D model with high speed, impeccable accuracy, and precision opens the possibility of developing personalized drug delivery systems based on patients' needs. Extrusion-based printing has garnered tremendous interest and radiates potential for developing pharmaceutical drug products owing to its low cost-effectiveness, customizability, on-site small-scale production, and flexibility of feed materials¹.

Pneumatic extrusion is utilized either for high melting point thermoplastic melt, as used in direct melt extrusion, or for extruding low melting point gels as employed in syringe-based extrusion.  Direct melt/ thermoplastic extrusion minimizes the two-step limitation offered by first-generation 3D printing techniques like FDM (Fused Deposition Modeling), which is rather unsuitable for thermolabile excipients and APIs. Multiple steps also elevate the chances of batch-to-batch variation with difficulty in formulation optimization. On the other hand, direct melt extrusion melt mix and extrude the selected excipients and API near their melting point range to fabricate the products conveniently with more consistency and ease. Melt extrusion is advantageous in fabricating immediate dosage forms like tablets, sustained release polypills, and long-acting products like drug-eluting polymeric implants, stents, and transdermal patches². This technique allows the designing of complex geometrics and shapes and aids in solving pharmaceutical concerns like poor solubility and bioavailability.

The primary concern with melt extrusion is the application of heat before extrusion through a smaller nozzle under pneumatic pressure. Such physical and thermal stress might not be appropriate for most of the APIs and excipients. In such cases, pneumatic extrusion without heat application has been primarily investigated to manufacture dosage forms like oral dispersible films(ODFs), solid lipid tablets, hydrogel patches, and microneedles³. The reduced temperature during printing makes it also the most biocompatible technology for cellular work and bioprinting. Pneumatic extrusion could be bestowed for creating physiologically relevant tissue models and organ-on-a-chip models using less viscous hydrogels loaded with bioinks. The hydrogels mimic the extracellular matrix and allow encapsulation of cells and bioactive molecules, forming cell-laden hydrogels for creating an in-vitro testing assembly, thus replicating animal models like corneal stroma, skin, bone grafts, and various organs. Natural hydrophilic polymers like alginates, chitosan, gelatin & cellulose and could be employed to prepare the biomaterial inks for the in-vitro models. The in-vitro models are yet to go mainstream in pharmaceutical industry due to technical challenges and regulatory limitations. Despite that fact, it is undeniable that pneumatic extrusion offers a plethora of opportunities to manufacture various drug delivery systems and testing models utilizing the concept of 3D modeling and fabrication.  

References:

1. Annaji M, et al. Application of Extrusion-based 3D Printed dosage forms in the treatment of Chronic Diseases. Journal of Pharmaceutical Sciences. 2020 Oct 6.
2. Lim SH,et al. 3D printed drug delivery and testing systems—a passing fad or the future?. Advanced drug delivery reviews. 2018 Jul 1;132:139-68.
3. Seoane-Viaño I et al. Semi-solid extrusion 3D printing in drug delivery and biomedicine: Personalised solutions for healthcare challenges. Journal of Controlled Release. 2021 Feb 27.

Keywords: 3D-printing, Pneumatic Extrusion, Drug Delivery