3D printing or additive manufacturing is a process of creating three-dimensional solid objects from a digital design. The process involves printing sequentially thin layers of the building materials until the object is created. The earliest 3D printing technologies came about in the 1980s. Over the past decades, 3D printing has proved itself to have the potential of revolutionizing the way we make almost everything. Nowadays, 3D printing has been employed in aerospace, manufacturing, construction, medicine, and biomedical engineering. Spritam®, the levetiracetam tablets made by 3D printing technology was first approved by FDA in 2015, which marked a new chapter of making drugs. 3D printing is largely for oral solid medications accounting for the majority of marketed drug products. More over, 3D printing is able to print small batches for small patient populations. The patient-specific or personalized 3D-printed medicine tailors treatments to the individual characteristics of each patient. Its simple and decentralized production process enables locally controlled supply chain without security issues such as contaminations and frauds, but on the other side, bings in new compliance and regulatory challenges. The 3D-printing drug manufacture has created a perfect storm for the pharmaceutical industry and its regulatory agency.
3D-printing Technologies in Pharmaceutical Applications
Although not yet fully commercialized as the traditional formulation technologies, the following methods are widely used in making 3D-printed drugs [Ref. 1]: Extrusion Molding Printing (EMP), Drop On Powder Printing (DOP), Selective Laser Sintering (SLS), Stereolithography (SLA), and Electrohydrodynamic Printing (EHD). In all techniques, the printing is executed by following the model parameters preset by a computer design. Among these established methods, DOP and EMP are well studied and have become common practices [Ref. 2]. For instance, DOP is successfully employed in the production of Spritam® tablets. However, Each method has its own pros and cons, and requires further fine-tunes or big-leaps in resolving technical incompetency.
The EMP technology has two branches based on molding materials, the fused deposition modeling (FDM) and semisolid extrusion molding (SSE). In FDM method, a semifluid state of drug-loaded polymers is formed by heating, which is then extruded from the printing nozzle. The desired product is formed after solidification. The cheap and simple operation process has made FDM the most frequently used technique. However, the high heating temperature, usually over 150 °C, is not suitable for thermal-liable APIs without adding low-melting point excipients or water in the drug-loaded filaments. In contrast, the SSE technology does not involve heating process, and can be a good surrogate technique for temperature-sensitive APIs. It extrudes semisolid paste under the pressure of screw gear rotation via a syringe-based print head, and deposits the paste in layers to form the object. One of the disadvantages of SSE is using organic solvents in preparing the paste, which can lead to the residual solvents in the printed products.
DOP is similar to wet granulation used in tablet preparation with regard to solidification mechanisms. DOP sprays droplets containing binders from the print head onto the powder bed. The API can be dispersed either in the liquid or solid phases, e.g. discharging excipient binder onto API-loaded powder. After printing one layer, the platform is lowered vertically, and the new powder layer is spread over the previous layer. The procedures are repeated until the dosage form is complete. This print-glue approach offers reduced formulation complexity, as similar binders are compatible with a broad range of APIs. The method is relatively low cost, easy to scale up and produces tablets with high porosity. The limitation of DOP is its low resolution and high fragility. Post-processing is needed to eliminate residual solvents and recovery of the unprocessed powder.
In SLS, CO2 laser beam instead of binder droplets in DOP is applied to sinter the selected regions of powders in each layer with precision. SLS offers high-resolution, solvent-free, single-step 3D printing. Its process chamber is generally kept ...
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