Overview of Pharmaceutical 3D printing
How 3D Printing is Transforming Pharmaceuticals into More Precise, Effective Treatments
3D printing is one of the most revolutionary technologies of contemporary life. It’s reducing manufacturing costs, personalising industries, and saving lives one innovation at a time. Computer-aided design files can be customised in a snip, so multifunctional drug delivery systems are finally possible. They can be processed so rapidly that even street corner pharmacists can handle them. Personalised medications are just on the horizon. The technology also tackles one of medicine’s most prominent issues: targeted therapies. In fabricating novel dosage forms on a massive scale, it’s making conventional drug delivery systems a thing of the past. Demand for patient-centric drug product development has been growing rapidly since 2015 when the first 3D printed pill was FDA-approved.
Types of 3D Pharmaceuticals
Pharmaceutical companies are constantly reaching for new innovations in drug design, focusing on material properties, processes, and technologies. 3D printed medicines have created innovations in all three categories, both to achieve personalised drug dosing and create a patient-centric product. They’re easy to fabricate and customise, and their cost-efficiency allows them to be pushed through small-scale production lines. Unnecessary resources and manufacturing costs are waylaid, and droplet sizes can be controlled well enough to create multi-dosing products. In inkjet printing, viscosity can be tightly controlled, making microcapsules possible. 3D technology has diversified to include:
Fused Deposition Modelling FDM
Here, polymers are melted, then pushed through a mobile, heated nozzle. A polymer is layered along the X, y, and z axes in a precise shape. This technology is used for implants, zero-order release tablets, and formulations that include polymers.
Thermal Inkjet Printing TIJ
Ink fluid is used to create a vapour bubble using a micro-resistor. The ink is forced through a nozzle, dispensing a solution onto three-dimensional scaffolds. Thermal inkjet printing TIJ can avoid heat by relying on voltage, so it can be used to print heat-sensitive medications.
Inkjet Printing
Powder is applied as a substrate, using variable layers and drug combinations. The ink is sprayed in various droplet sizes, drying to provide a solid dosage form. Unlike thermal inkjet printing TIJ , clogging is unlikely and a continuous flow can be achieved.
Direct-Wise
A 3D microstructure is created through a pattern-generating device. A computer-controlled translational stage guides the process.
Zip Dose
Personalised 3D printed medicines with a high drug-load are produced using porous material. The procedure relies on high dissolution and disintegration levels.
Vat Photopolymerization
Light-induced polymerization uses light irradiation to cure liquid resins in layers for controlled release. Two-dimensional layers are cured into a hardened 3D structure with drug delivery potential.
3D technology has already crept into the marketplace in the form of polypills, excipients, nanosuspensions, and hydrogels. Post-market examples include:
- Aprecia Pharmaceuticals’ Spritam: An epilepsy drug produced in layers until the correct dosage is achieved.
- Guaifenesin: A bi-layered polypill with controlled release.
- Nifedipine, captopril, and glipizide: A multiactive polypill containing multiple active ingredients relying on extrusion-based printing.
- Ibuprofen hydrogels manufactured using stereolithography to create a temperature-responsive delivery process.
- Progesterone A selective layer sintering process has been used to create a drug delivery device.
- Pseudoephedrine: Binder jet printing is used to create a cubic tabular device.
- A folic acid nanosuspension created with inject 3D technology.
- Salbutamol sulfate solution printed using thermal inkjet technology.
Watch our video about 3D printing here:
Approaches to 3D Technology
Today’s medications are prepared using the most popular dosage forms, giving doctors little control over their prescriptions. Personalised 3D printed medicines can be adjusted by their therapeutic value, so doctors can treat their patients rather than the numbers pharmaceutical companies find convenient. In addition, complex drug release profiles allow manufacturers to fabricate complex, porous layers with their own barriers to control release. 3D technology has even been used to create drug implants that release chemicals at specified times.
The first 3D printed product was developed in 1981, but its inventor couldn’t have imagined the seismic waves it would send through the industrial design industry. Its effects on the healthcare industry have been, perhaps, the most surprising. By 1998, NHS Hospitals throughout the UK had used it to create surgical guides and tools, and today, CAD software is been used to print scaffolds for organs, tissues for implants, and structures for orthopaedic care. The first Spritam tablet rolled off production lines in March 2018. Within only a few years, the pharmaceutical industry has developed several unique medical applications that might one day do away with production lines entirely.
The Medical Applications of 3D Printing Procedure
In April 2020, The International Journal of Pharmaceutics’ researchers attempted a partial coating using a semi-solids 3D printer. Their goal was to tune the release of two ingredients without altering the composition of the drugs themselves. They were successful, partly thanks to 3D technology’s ability to combine different dissolution profiles. 3D tablet coating can exploit Fickian diffusion — a characteristic polymer relaxation process. This isn’t the only tablet coating application 3D technology has achieved. It can also use fused deposition modelling FMD to create enteric polymers with precise drug loading quantities and infill percentages. Oral solid dosage forms are less than ideal for absorption via the gastrointestinal tract. Scientists have been trying to improve colon drug delivery for decades, and 3D printers are finally making it possible.
The Benefits of 3D Medical applications in the Pharmaceutical Industry
1) Dosage-Specific Parameters
Zip Dose technology is merging the implant and drug delivery worlds, and this has, at last, made site-specific colon targeted drugs a reality. Drop-on powder has also been used for the anti-cancer drug, fluorouracil. Researchers recently tested a range of polymer solutions to achieve just the right dosages via fused deposition modelling FMD. This research proved that optimised powder-based printing could produce excipients without thermal processing, thereby allowing thermo-sensitive drugs to be produced in precise dosages. The study’s printing parameters included binder volumes, jet dispenser speeds, and the number of drops fired. Production kept temperatures below 50 degrees Celsius. Drop on demand techniques ultimately produced a homogenous coating that required nothing more than the right carrier powders.
2) Micro-Dosing Without Oxidation
Breaking up tablets can oxidise ingredients. When drugs need to be quartered, accurate dosages are well-nigh impossible to achieve. 3D-printed options can offer unique dosage forms that deliver microdoses without oxidation risk.
3) Increased Solubility
Why limit 3D printing to metal and plastic when you can leverage the technology to print active ingredients in a way that improves efficacy? Thermal inject printing TIJ has been used to manufacture Miconazole, which has notoriously low solubility in aqueous environments. TIJ micromolding uses coated microneedles as drug-loaded coatings. 3D-printed drug delivery devices like microchips and polymeric nanoparticles have become cheap enough for mass consumption. Vat photopolymerization is used in a similar way by relying on light-activated polymerization for unique drug-delivery applications. Zip Dosing takes solubility to an entirely new level by achieving a rapidly-disintegrating formulation. Researchers are currently looking into what hot-melt extrusion and drug geometry changes will do for drug release.
4) Faster Trials
Medical engineers have used vat photopolymerization and other 3D technologies to create pre-clinical medications for trials. This process is much faster than has ever been possible before. As testing accelerates, so does pharmaceutical innovation. Pharmacists are changing drug design on-the-fly directly from a CAD file. This allows the last link in the supply chain to create new iterations to salt forms, dosages, and excipients when required.
5) Unique Dosage Forms On-Demand
Unique dosage forms can be achieved through authorised blueprints. This gives pharmacists the power to shorten the supply chain. Distribution and logistics costs can be eliminated this way, and medical practitioners can treat several illnesses in a single tablet.
6) Non-Contact Processing
Inkjet printing can process up to 100 pl droplets into 3D structures through a micrometre-scale nozzle. The liquid can be heated to boiling temperature or exposed to voltage. This way, contamination and heat damage can be minimised, but inkjet technology can do more than just build layers. It can also be used to print magnetic nanoparticles, purified protein arrays, and other biological materials. Drug release profiles can be strictly controlled through consistency, filtration, and pH levels. This technology has been used to create prednisolone solid dosage forms with the help of heat and extra polymorphs.
7) Repeatable Accuracy
3D printed methods offer more resolution, accuracy, and repeatability, even for small-scale production lines. This will become a great equaliser in the pharmaceutical industry as small businesses gain the ability to create complex products on tight budgets. Unnecessary resources can be eliminated, and that should be felt in the final consumer price. Better yet, with complex drug release profiles comes a heightened degree of control over drug delivery. This can even improve the efficacy of some medications.
The Case for Chemotherapy
Chemotherapy drug delivery is notorious for its imprecision, but 3D printed absorbers and excipients are improving the field. Toxicity is one of its most overt problems, so scientists have developed 3D printed porous absorbers that can capture the drug in the bloodstream immediately after it’s been exposed to a tumour. They used a coated, nanostructed copolymer sandwiched between a doxorubicin binder. The absorbers were deployed, then captured using image-guided endovascular surgery. The procedure was minimally invasive and went a long way towards reducing side effects. This allowed researchers to use higher doses of Doxorubicin than was possible before, increasing cell death while minimising side effects like cardiac failure. 3D print technology is fast and economical enough to allow doctors to create custom absorbers specific to each patient’s anatomy.
Personalised 3D Printed Medicines
The 3D printing procedure is an elegant solution to personalised drug dosing. Zip dose technology is the forerunner in this area, having been developed for 3D-printed pioneer, Spritam. An inkjet process can layer powdered medication in tiers without compression or classic moulding techniques. In the coming years, pharmacists will be able to print medications unique to every patient, but personalisation’s rewards aren’t limited to dosage alone. Various drugs can be combined in a single pill, helping patients to become more compliant with their prescriptions. Direct-wise 3D microstructures are perfect for that purpose. The technology can be used to manufacture patient-specific medications in custom combinations. Personalised medications are already being manufactured for both customised dosages and formulations. The days when patients had to swallow several pills at a time will soon be over. Mass manufacture will soon be a thing of the past, and the effects are going to send seismic waves through the pharmaceutical industry.