Personalized 3D Printed Drug Delivery Systems By 3D Scanning

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.

3-dimensional printing (3DP) of medicines is becoming an increasingly popular trend, especially since the first 3D printed medicine (Spritam®) was approved by the FDA in August 2015.

Researchers from University College London – School of Pharmacy and FabRx Ltd. have recently published a paper in International Journal of Pharmaceutics in which they show, for the first time, the fabrication of oral tablets by stereolithography.

Graphical abstract of the article.

Stereolithography (SLA) is a type of 3DP technology, based on the solidification of a liquid resin by photopolymerization. A laser is focused on to a specific depth in a vat of resin, causing localized polymerization (and so 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.

In a previous study, approximately 50% of the model drug 4-aminosalicylic acid (4-ASA) was degraded during 3D printing.

In this study, paracetamol (called acetaminophen in US) and 4-aminosalicylic acid (4-ASA, used in the treatment of inflammatory bowel diseases) were selected as model drugs. The drugs were 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, USA).

Form 1+ SLA 3D printer

A torus design (donut shape) was selected as the template to print the tablets due to its complexity compared with conventional tablets shapes, and because of its difficulty in manufacture by current production techniques, such as powder compaction.

Template used as a model for printing tablets

Tablets containing the drugs were successfully produced with the SLA printer and various formulations with different properties were fabricated. No drug was degraded during the 3D printing process what is especially relevant for 4-ASA since its degradation using FDM 3D printing has been previously reported. A major advantage of SLA printing is its versatility, as drugs can be mixed with the photopolymer solution prior to printing, and become trapped in the solidified matrices. Other advantages over FDM 3DP is that the printing is a one-step method, without need of previous processes, just dissolution of the drug in the printing solution.

3DP tablets loaded with 4-ASA (brown colour) and paracetamol (white colour).

The in vitro dissolution test performed in a realistic dynamic dissolution simulation of the gastrointestinal tract shows that drug release from the tablets commences in the gastric phase and continues during the intestinal phase for all formulations and it was dependent on the composition of the formulations.

According to the authors, this technology offers a simple, fast method to fabricate drug-loaded tablets with high resolution. Compared with FDM 3D printing, SLA printing reduces drug degradation and so offers an alternative route to produce tablets incorporating thermo-sensitive drugs.

SLA 3DP technology may allow the manufacture of drug loaded tablets with specific extended-release profiles. In the future this technology could become a manufacturing technology for the elaboration of oral dosage forms, for industrial production or even for personalised dose.

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