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Lepowsky E and Tasoglu S

manufacturing also introduces precise and unique for a 3D printing medium, as well as for a drug carrier.
dosing, and the ability to create multi-dose or multi- Hydrogels also exhibit a diverse range of controlled re-
[99]
drug pharmaceutical products. Dosing may also be lease functions . As a material property, many hydro-
tailored specifically for individual patients. Similarly, gels are biodegradable over time, which lends itself to
the printing of drugs makes point-of-care, pharmacy- taking advantage of polymer dissolution as a form of
based drug production possible, without the risks controlled release. Additionally, due to the high diffusion
and extensive fabrication time associated with com- of hydrogels, they may also be leveraged for diffusion-
pounding pharmacies. These benefits of 3D printing controlled release and swelling-controlled release.
for drug manufacturing pave the way for the future of Finally, hydrogels are also compatible with chemically-
pharmaceuticals (Figure 2). controlled release.

4.1 Release Characteristics of Drugs 4.2 Precise and Unique Dosing
The release characteristics of a drug refer to the quantity 3D printing of drug products enables a newfound level of
of the loaded drug that is emitted from the dosage form customization and personalization in drug dosing that is
with respect to elapsed time. This has a significant im- nearly impossible using typical commercial, mass-scale
pact on the application and relative effectiveness of the production methods. Presently, proper dosing is often
medication. One manner of manipulating the release imprecise, which can have costly results, in terms of
characteristic of a drug is the geometric design and both money and health [100] . While clinical pharmacology
archi tectural complexity of the drug product. 3D printing studies have been conducted to improve methods of drug
is an ideal method for increasing the geometric and dosing control and to help doctors prescribe the correct
architectural complexity of dosage forms. 3D printing dose on a patient-to-patient basis, less work has focused
allows for custom-designed, discrete shapes to be fa- on the production of the prescribed doses. 3D printing
bricated, each with its own respective release timing. offers highly-precise fabrication, in addition to the
For instance, tablets of various shapes prepared with a capacity of unique dosing, all attributed to the free-form
constant surface area-to-volume ratio display different nature of 3D printing.
drug release rates, from fastest to slowest: sphere, cube, Exemplifying the application of 3D printing to pro-
torus, cylinder and pyramid [93] . These findings are the vide precise dosing, a flexible-dose dispenser was
result of drug diffusion and polymer dissolution [94,95] . developed that combines FDM 3D printing with hot melt
The predominance of one of these factors over the extrusion (HME), which is a common pharmaceutical
other depends on the tablet shape and the solubility of manufacturing process [101] . HME was implemented to
the drug that is loaded in the tablet. This information produce drug-loaded filament by accurately mixing
can be leveraged with the capabilities of 3D printers the drug with the filament material via a twin-screw
to manufacture drugs with purposeful geometries compounder, thereby providing digital control over the
for different release characteristics; in particular, by concentration of drug melted into the filament. Following
diverging away from typical spherical forms, 3D printing the HME process, the drug-loaded filament was used in
for drug manufacturing enables different and more a FDM printer to direct-write pharmaceutical tablets,
[96]
precise drug delivery functions . which also introduces a high level of digital control
In addition to creating complex architectures of drug through the design of the 3D printed tablets. Leveraging
carriers, 3D printing is also capable of fabricating multi- the linear relationship between the mass and volume of
layer delivery systems. Bilayer tablets are common for printed tablets, tablets of varying doses were able to be
controlled release delivery systems, by incorporating printed with high precision.
instant-release and slow-release layers in the same Digital control over drug dosing is not limited to
dosage form. While bilayer tablets are not a novel FDM 3D printing; it has also been demonstrated with
pharmaceutical product, the ability to fabricate them in hydrogels which are compatible with inkjet printing.
essentially a single step by means of a 3D printer may Following the deposition of drug-loaded hydrogel
revolutionize the process . Furthermore, controlling the material, the hydrogel is cured by exposure to ultraviolet
[97]
release timing by printing the carrier in different shapes (UV) or near-UV light, which causes photo-initiator
and densities may also contribute to greater control over embedded within the material to crosslink. This photo-
burst release, which is the phenomenon of excess drug sensitive crosslinking may be utilized as a mean of
being released upon initial contact with the dissolution digital drug dosing by using a projector to precisely cure
[98]
media . a portion of the printed hydrogel [102] . The cured portion
A final and important consideration for the release of the hydrogel forms the drug dose, while the uncured
characteristics of drugs is the material of the drug hydrogel can be washed away.
carrier. As described above, hydrogel is a great candidate 3D printing for drug manufacturing also advances

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