Currently, millions of people consume prescribed medications, daily, for the treatment of different diseases. There are some treatments in which, in order to keep the safety of the patient, the exact dose of drug is necessary, but not all drugs contain the desired dosage according to each person, since these are manufactured massively and they do not always manage to cover the needs of each of the patients. And it is because of this lack of supply, that it became important for the industry to start the research of a more personalized medicine, which highlights the individuality of each patient and leaves no room for error in the dosage, as it can affect the performance of some treatments.

Benefits of 3D printing in patients

3D printing could bring benefits to many patients. First of all, for polymedicated patients, since a single pill can be created by combining different active ingredients. This is done by dividing a single tablet into different compartments and in each of these the drugs that the patient needs are printed.

It could also have advantages for younger patients, since there are many oral medications that are not adapted for children and they have hard times swallowing. With this new technology, it would be possible to print smaller and easier-to-swallow tablets and, in this way, facilitate treatment for this group of younger patients.

It could also be useful for patients with rare diseases, who are less likely to have access to treatment due to the small population with the same disease. 3D printers offer the possibility of being installed in pharmacies, hospitals and clinics enabling the production of medicines on demand, with particular advantages for drugs with low stability or that require a cold chain.

However, this type of practice is not so simple: on one hand, it is necessary to train health professionals; but also the 3D printers used in these facilities must have very high quality standards and they must be able to be cleaned very well so that there is no contamination.

It is because of these difficulties that, so far, the first and only drug printed with 3D technology is Spritam (levetiracetam), an antiepileptic drug manufactured by Aprecia Pharmaceuticals, which in 2015 received approval from the FDA (Food and Drug Administration).

This orodispersible tablet disintegrates in seconds when it comes in contact with liquids and, also, it is possible to achieve a higher dose than with conventional methods.

This pill is manufactured using Aprecia’s proprietary ZipDose technology, which is based on using a “drop-on-solid” printing technique in which drops of a liquid binding agent are deposited by a printing nozzle onto a pharmaceutical powder base, unifying it. The base is then lowered to allow another layer of powder to be added. This process is repeated systematically, introducing more drops, thus adding height to the pill, while the surrounding unbound powder particles act as a supporting structure to prevent the collapse of the highly porous structure of the pill.

3D printing technologies and the interest of the pharmaceutical industry

There are various 3D printing technologies, which differ in 3 aspects:

• The materials used in manufacturing
• How layers are created
• How some layers link each other.

Of all of them, the ones that have the interest of pharmaceuticals are stereolithography (SLA), fused deposition modeling (FDM) and pressure-assisted microsyringe (PAM).

Stereolithography (SLA)

It is based on the principle of photopolymerization that consists of the liberation of free radicals by the interaction between the photoinitiator (carbon monomers that integrate the liquid resin) and UV light. This causes the resin or other chemical materials to solidify, thus creating strong unbreakable bonds with each other. This technology is the one that best allows the combination of different drugs in the same 3D container, since different active ingredients can be incorporated into the polymer network.

Fused Deposition (FDM)

Fused deposition modeling is one of the most used techniques in various fields and, specifically, in the pharmaceutical and medical sectors. It consists of depositing a molten plastic polymer on a flat base, layer by layer, through an extrusion nozzle according to the 3D digital model supplied to the printer.

It has the ability to make combinations of multiple drugs (polyps), as well as sustained or delayed-release tablets.

One of the challenges that this technique presents is the meticulous adjustment of the temperature so that it does not affect the active principles that are deposited in the pill.

Pressure Assisted Microsyringe (PAM)

It is a very similar technique to FDM, but unlike the latter, it uses viscous materials instead of melts. It is based on the layer-by-layer formation of 3D objects by extruding a viscous polymer ink onto a platform. The material is extruded at room temperature, mechanically or by pumping pressurized air into a syringe.

It is mainly used in complex drug delivery systems, as it usually requires a small amount of samples.

The challenges of 3D medicine

Although we are still in an early stage in the development of 3D medicines, the future of these new medicines could be promising and, with their correct use, change the course of traditional medicine to a more personalized medicine focused on the individual needs of each patient.

However, the importance of submitting these developments to the strict regulations of the pharmaceutical industry should not be overlooked. Since, like the arrival of many new technologies, a misuse of drug printing could lead to harm in many patients.

Another challenge currently presented by this mechanism is the high cost of drug printing. In part, because they are still aimed at a reduced mass of people, but also because they are affected by the initial stage of development in which this technology is right now, making it difficult to compete in the economic aspect against drugs that are manufactured in large volume, benefiting from economies of scale.

Is there a promising future for 3D medicine?

3D medicine has advantages that could make 3D printing a key element of personalized medicine:

• The possibility of adjusting the doses of the active ingredients
• The ability to design the geometry, shape, size and flavor of the formulation
• The incorporation of several active ingredients in a single tablet or capsule with different release profiles.

With all this, adherence to treatment would be improved, mainly in polymedicated, geriatric and pediatric patients.

Additionally, making more personalized treatments will reduce costs and minimize waste, involving more efficient, profitable, and above all, sustainable supply chains, one of the most important trends for all industries today.

However, 3D printers still have obstacles to solve and a long way to go until they will be fully operating in hospitals and clinics.

References:

https://www.tipt.com/blog/innovations-in-dosage-forms-to-pay-attention-to-if-youre-in-pharmaceutical-training/

https://www.pharmoutsourcing.com/Featured-Articles/574136-Defining-the-Future-of-Drug-Dosage-Forms/

https://manufactura.mx/industria/2014/02/07/nuevas-formas-de-tomar-tu-medicina

https://gacetamedica.com/investigacion/nuevas-formas-de-medicamentos-si-se-puede-imaginar-se-puede-hacer/

https://www.pharmtech.com/view/new-dose-forms-focus-patient-0

https://pubs.rsc.org/en/content/articlelanding/2014/tb/c4tb00548a

https://www.3dnatives.com/es/medicamentos-impresos-en-3d-140520202/#!

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https://www.medicaldevice-network.com/comment/3d-printing-drugs-personalised-medicine-sustainability/