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3D printing for drug manufacturing: A perspective on the future of pharmaceuticals

drugs can be covalently or physically linked to the area in its permanent shape but a compact, low surface
hydrogel network to limit the drug’s release, whereas area shape in its temporary shape; the drug would be
this is impossible in FDM [74,75] . Drug release would only ingested or implanted while in its compact shape, and
occur as the bond between the drug and hydrogel, or the once in the targeted location, external stimulus would
hydrogel itself, degrades. It is important to note, though, cause the transformation to its high surface area shape to
that degradation of hydrogels often occurs primarily by allow for high drug release rates.
bulk degradation, as opposed to surface degradation, Importantly, researchers have shown that the incor-
due to high diffusion; surface erosion would be made poration of drugs does not have a significant impact on
possible by further modification and careful selection of the thermo-mechanical behavior and shape memory
the hydrogel materials [76–78] . properties of the SMPs [86,87] . Furthermore, SMPs exhibit-
ing biodegradability and zero-order drug release have
3.4 Smart Materials for Drug Delivery also been developed [79,88] . By leveraging the elas tic
Drug delivery can greatly benefit from smart materials properties of particular SMPs combined with hydro-
which are compatible with 3D printing. More spe- phobic materials, SMPs can be designed to release
cifically, smart materials of interest include shape drugs without an initial burst followed by hydrolytic
memory materials and environment-stimulated materials degradation. Another exemplary implementation of
[89]
such as pH- and temperature-sensitive materials. In SMPs is for double layer delivery systems . A multi-
general terms, degradable shape memory polymer layer approach allows for finer tuning of drug release,
(SMP) are multifunctional materials which are designed while still maintaining the mechanical properties of
to conform to their therapeutically relevant shape and an elastic material ideal for implantable applications.
mechanical properties after implantation [79] . SMPs are With a focus on drug eluting implants, SMP stents
considered active polymers, as they change from a have been designed to perform a double duty: provide
temporary shape to their original, permanent shape upon the mechanical function of an implantable stent while
exposure to a stimulus. This controllable, conformable simultaneously delivery drugs [90] . By adding the drug
change can be leveraged for drug delivery. Most com- eluting feature to SMPs, implants and stents can be
[91]
monly, the stimulus is in the form of a temperature designed with anti-inflammatory agents built-in .
change, i.e. the internal temperature of the human body 4. Benefits of 3D printing for Drug Manu­
compared to the outside temperature. pH-sensitive ma- facturing
terials are also very useful in designing SMPs: due to
the dependence on the physiological environment of the Once an appropriate 3D printing method is determined
drug, pH sensitivity can act as a reversible switch for and the material best suited for the pharmaceutical
drug release as the drug form migrates through the body application is selected, it is a matter of developing and
or as the environment changes in acidity/alkalinity [80] . printing the drug itself. It is at this stage in the drug
Other possible stimuli include light, pressure, or a mag- manufacturing process where 3D printing presents itself
[81]
netic or electric field . as the ideal approach, attributed to some noteworthy
When considering the printing of SMPs, it is often benefits [92] . One of the primary considerations in the
referred to as four-dimensional (4D) printing, wherein delivery of drugs is the release characteristics. 3D
the fourth dimension is time [82–85] . After 3D printing printing enables increased geometric and architectural
the drug form, the printed drug can change its shape or complexity, facile fabrication of multi-layer delivery
functionality when the external stimulus is applied. For systems, and the application of various controlled
instance, a drug form can be printed that has high surface release mechanisms. Printing as an approach for drug

Figure 2. Theoretical scheme of 3D printing for drug manufacturing. Based on a patient’s specific prescription from his doctor, a custom
medication is designed via computer-aided design. The dosage form may be composed of complex geometries, multiple doses, or even
multiple drugs. Drug-loaded bioink (biocompatible material) is then 3D printed on-demand.

6 International Journal of Bioprinting (2018)–Volume 4, Issue 1