In recent years, 3D printing technology has achieved certain accomplishments in the field of pharmaceutical formulation printing, with tablets, sustained-release and controlled-release formulations, and drug delivery systems emerging as research hotspots. In August 2015, the first 3D-printed drug, Spritam (levetiracetam), designed by Aprecia Pharmaceuticals, was approved by the FDA for marketing. This drug is produced based on the company's ZipDose 3D printing technology platform. The levetiracetam fast-dissolving tablets prepared using ZipDose technology possess porous characteristics, enabling them to disperse in water to a much greater extent than traditional tablets. Moreover, they dissolve with just a sip of water.

Currently, the 3D printing technologies used in the pharmaceutical formulation field primarily include Fused Deposition Modeling (FDM), Selective Laser Sintering (SLS), Stereolithography (SLA), and Thermal Inkjet Printing (TIJ). Among these, FDM technology is the most widely applied in the formulation field, with commercial FDM printers and printing software commonly used for the preparation of tablets, sustained-release, and controlled-release formulations.

Pharmaceutical Excipients for 3D Printed Dosage Forms

The basic principle of 3D printing solid dosage forms involves fused deposition modeling (FDM) and deposition molding. However, not all molten materials are suitable for use in pharmaceutical formulations. The extrudable consumables used in 3D printed pharmaceutical formulations must be harmless when ingested by humans or easily excreted by the body, thus placing high demands on the materials. Commonly used materials include mixtures of copovidone VA64 and AffinisolTM15, hydroxypropyl methylcellulose, polycaprolactone, ethylene-vinyl acetate copolymer (EVA), and polyvinyl alcohol (PVA).

Copovidone is a water-soluble polymer resin in the form of a white powder, odorless and tasteless, soluble in non-polar solvents such as water, ethanol, and anhydrous alcohols, and possesses excellent adhesive and film-forming properties along with good surface activity. Some scholars have used different polymers such as copovidone VA64, AffinisolTM15, and polyvinyl alcohol-polyethylene glycol copolymer mixed with drugs for hot-melt extrusion to prepare materials suitable for printing. The results showed that a 1:1 mixture of copovidone VA64 and AffinisolTM15 is an appropriate polymer system for 3D printing and rapid drug release.

Hydroxypropyl methylcellulose (HPMC) is safe and non-toxic, and is commonly used as an excipient in pharmaceutical formulation processes. By using HPMC as the main excipient, mixed with Soluplus and the active pharmaceutical ingredient, and undergoing melt extrusion, consumables for printing drugs can be prepared and printed into controlled-release tablets with a smooth surface and dense structure.

Polycaprolactone (PCL) is a novel resin with excellent biocompatibility and biodegradability. It is currently used in controlled-release drug carriers and medical surgical sutures. Using PCL as the main polymeric compound to prepare 3D-printed tablets containing polymeric nanocapsules, it has been found that the combination of nanotechnology and 3D printing technology can integrate their respective advantages, enabling the use of personalized manufacturing methods to customize drug release profiles and dosages, as well as controlling drug release rates at the nanoscale.

Ethylene-vinyl acetate copolymer (EVA) is a new environmentally friendly plastic foaming material that is non-toxic and odorless. By using different specifications of EVA as the main excipient and adding it to the active pharmaceutical ingredient (API) for hot-melt extrusion, the extruded filaments can be analyzed and studied using scanning electron microscopy (SEM), infrared spectroscopy (IR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and in vitro drug release methods to investigate the crystal form and release rate of the API in the extruded material and the printed solid dosage forms. The study found that the obtained drug was more easily released from the surface of the fibers, forming spores in their external regions.

Polyvinyl alcohol (PVA) is a polymeric organic compound that is non-toxic and has no side effects on the human body, exhibiting excellent biocompatibility. In pharmaceutical formulation research, it can be used to prepare water-soluble gels for ophthalmic applications. Its aqueous gels have extensive applications in ophthalmology, wound dressings, and artificial joints. Additionally, PVA films are also used in medicinal films and artificial kidney membranes. Using hot-melt extrusion (HME), fibers containing budesonide have been successfully prepared, with the budesonide loading in the fibers being significantly higher than that achieved through alcohol solution-based solubilization. Thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) data confirm that budesonide does not degrade during the HME process.

3D Printing and Pharmaceutical Formulations

Compared to the application of 3D printing technology in drug synthesis, commercial 3D printers and existing software are more suitable for the preparation of pharmaceutical formulations, especially for tablets and controlled/sustained-release formulations. The use of 3D printing technology in drug preparation offers several significant advantages over traditional methods: ① Rapid prototyping speed; ② The ability to achieve precise shaping and local micro-control of multiple materials; ③ No waste of raw materials; ④ More precise production. The integration of pharmaceutical technology with 3D printing technology has the potential to realize on-demand "made-to-order" drug production. In the future, doctors can prescribe digital prescriptions for patients based on their diagnoses and simplify the prescription information into a barcode. Patients can then use this barcode to print their medications via a 3D printer and take them for treatment. The use of 3D printers for drug production enables on-demand preparation, making drug production more precise and potentially reducing or eliminating the need for drug inventory, thereby solving drug storage issues.

3D Printing and New Drug Development

New drug development serves as a reflection of a country's economic and technological strength in the pharmaceutical industry, and its research status directly impacts the survival and growth of the national healthcare sector. In new drug development, many late-stage clinical trials fail due to the disparities between animal models and human tissues. To address this issue, researchers have adopted approaches to construct more complex tissue models in vitro that better mimic in vivo conditions, and utilize these tissue models for new drug screening and testing. However, constructing living organ tissue models using traditional methods is highly challenging. With the advancement of science and technology, 3D printing technology has emerged as a means to print living organs, such as livers and blood vessels. Applying 3D-printed living organs to new drug screening and testing will facilitate the creation of novel drugs and provide an entirely new approach to new drug development.

About the Author

Xiaonisha, a food technology professional holding a Master's degree in Food Science, is currently employed at a prominent domestic pharmaceutical research and development company. Her primary focus lies in the development and research of nutritional foods, where she contributes her expertise and passion to create innovative products.