3D Printing Medicines (Review articles)

We have recently published three interesting reviews in collaboration with University college London (UCL) about different aspects of the applications and challenges of 3D printing in the pharmaceutical sector.

You can find the articles following the links below. Contact us for reprints or to talk about new applications.

Fused deposition modeling (FDM) 3–Dimensional (3D) printing is becoming an increasingly significant technology in the pharmaceutical sciences, since it allows the manufacture of personalized oral dosage forms by deposition of thin layers of material. FabRx, in collaboration with researchers from University College London – School of Pharmacy, University of Santiago de Compostela and Astellas, have recently published a research paper in the International Journal of Pharmaceutics in which the effect of the internal structure -micropore volume- of drug loaded 3D printed capsule-shape tablets (Printlets™) on drug dissolution behaviour was studied.

Graphical abstract of the article.

A filament extruder was used to obtain filaments of polyvinyl alcohol (PVA) containing paracetamol (acetaminophen) or caffeine appropriate for 3D printing. The filaments were used to manufacture Printlets™ for oral administration using a FDM 3D printer.

The micropore volume of the Printlets™ was primarily determined by the presence of large pores due to gaps in the printed layers/net while printing, and the porosity of the Printlets™ was 10 fold higher than the porosity of the extruded filament.

A scanning electron microscopy image showing the internal structure of a cross-section of a Printlet™ and an image of the cross-section of a low dose paracetamol Printlet™ after porosity analysis.

Dynamic dissolution drug release tests on the Printlets™ in biorelevant bicarbonate media revealed distinctive release profiles, which were dependent on drug solubility and drug loading. Porosity of the Printlets™ bore no relevance in predicting the different drug release profiles.

Response surface for percentage of drug released 270min (D270) as a function of drug content in the formulation and drug solubility.

This study helps to elucidate which factors influence drug release from this type of new dosage form and confirms the potential of 3D printing to fabricate Printlets™.

The use of 3-dimensional printing (3DP) in the healthcare industry is becoming an increasingly popular trend. The FDA approval, in August 2015, of the first 3D printed medicine (Spritam®) proved that 3DP technology works and the race is now on to push forward its development in the pharmaceutical field.

Researchers from the UCL School of Pharmacy and FabRx Ltd., a pharmaceutical biotech specialized in 3D printing, have recently published a paper in the Journal of Controlled Release in which they demonstrate that the combination of 3D printing and 3D scanning has the potential to produce personalised drug loaded devices that can be adapted in shape and size to individual patient requirements.

Graphical abstract of the article.

In the study, 3D scanning technology was used to obtain a 3D model of a nose adapted to the morphology of an individual.

Sense 3D scanner (3DSystems) and templates used as models for printing.

Two different 3D printing technologies, Fused Deposition Modelling (FDM) and stereolithography (SLA), were used to produce flexible, personalised-shape anti-acne drug loaded devices.

Images of a MakerBot Replicator 2X FDM 3Dprinter and a Form 1+ SLA 3D printer.

In Fused-deposition modelling (FDM), an extruded polymer filament is passed through a heated nozzle that softens the polymer. It is then deposited on a build plate, in the x-y dimensions, creating one layer of the object to be printed. The build plate then lowers and the next layer is deposited. In this fashion, an object can be fabricated in three dimensions, and in a matter of minutes.

Stereolithography (SLA) is a type of 3DP technology, based on the solidification of a liquid resin by photopolymerization. A laser is focused, to a specific depth, on a vat of resin, causing localized polymerization (and thus solidification). Solidification is repeated in a layer by layer manner until a solid, 3D object is produced. SLA is superior to other 3DP techniques in terms of resolution.

Salicylic acid, used in the treatment of acne, was selected as a model drug in the study. The drug was incorporated in the filaments used in the FDM printer. The filaments were loaded into a commercial 3D printer, MakerBot Replicator 2X (MakerBot), and used to print the selected shapes. In the case of the SLA printer, the drug was added to the solution of monomers and the resulting photopolymer solution was loaded into the 3D printer, a commercial Form 1+ SLA 3D printer (Formlabs Inc).

Both FDM and SLA technologies enabled printing of nose-shape masks, whereas during the printing process using the FDM printer, part of the drug was degraded due to the high temperatures involved in the process. However, the SLA printer led to 3D printed devices (nose-shaped) with higher resolution and higher drug loading than FDM with no drug degradation. The in vitro results of drug permeation tests showed drug diffusion from all the 3D printed devices.

Image of 3D printed nose-patch loaded with salicylic acid.

According to the authors, the combination of 3D scanning and 3D printing could potentially offer the means to produce personalized drug-loaded devices that can be adapted in shape and size to individual patients’ requirements. These technologies offer a simple, fast method to fabricate personalized drug-loaded devices with high resolution. Compared with FDM 3D printing, SLA printing reduces drug degradation and so offers an alternative route for the production of devices incorporating thermo-sensitive drugs.

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