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Lepowsky E and Tasoglu S

(Figure 1D), and extrusion-based printing (Figures cyclically produce brief spikes in thermal energy which
1E and F) are ideal approaches for printing for drug is transferred to the ink [34] . The increase in thermal
manufacturing. energy causes the formation of a small bubble, which
provides a pulse of pressure to force ink out of the
2.1 Powder-Based Printing nozzle, thereby producing a droplet [4,35] .
Powder-based printing methods are the most similar An alternative to thermal inkjet printing is the piezo-
3D printing method to the common drug manufacturing electric approach, which implements a piezoelectric
method of powder pressing, in which a bed of powder is actuator to form droplets. A piezoelectric crystal within
pressed into a pre-fabricated mold. By the SLS method, a the print head is stimulated when voltage is applied,
[4]
thermal-sensitive powder is spread over the build surface which induces a rapid, reversible deformation . This
by a roller and pressed to form the appropriate layer deformation propagates acoustic waves which supply
[27]
thickness . After the layer of powder is established, a the pulse of pressure needed to disrupt the flow of ink
laser supplies thermal energy to the powder to stimulate through the print head, thereby producing droplets.
the melting and bonding of powder into the desired The inkjet printing method can further be applied
[28]
form . This process of spreading powder followed by to microvalve-based 3D printing. Microvalve printing
laser sintering is repeated for each successive layer. SLS utilizes a motorized stage comprised of an array of mi-
also allows for partial sintering, and the encapsulation of cro valves which are capable of depositing droplets of
non-sintered material within a sintered shell. material [36–38] . Each microvalve is connected to its own
An additional powder-based method is binder depo- pressure regulator, allowing for individual con trol of each
sition [29–31] . Following the same procedure for powder one. By controlling the stage and the pres sure regulators
spreading, binder deposition is an additive method in unison, various materials can be simultaneously
that builds from a bed of powder layers. Instead of a deposited. This scheme has been previously applied to
laser melting the powder as in SLS, a binder solution is cell-laden bioprinting, whereby support material, growth
[37]
spotted onto the powder. This binder solution dissolves media, and cell-laden material were printed together .
the powder which then re-crystalizes to form the solid Microvalve-based 3D printing can be applied to drug
form. By this method, the drug ingredients may either be fabrication by depositing various drug-loaded materials
mixed in with the powder, or the drug may be mixed into along with binders, scaffolds, and other biodegradable
the binder solution. materials.
2.2 Stereolithography 2.4 Extrusion-Based Printing
Similar to SLS, stereolithography utilizes a laser or Extrusion-based printing entails the extrusion of a
projector to solidify material while in a bulk setting. continuous stream of ink, as compared to the droplets
With stereolithography, also known more generally as which are formed via inkjet printing. By using this
photo-polymerization, the drug would be dissolved into method, the substrate material is mixed with the drug
a liquid pool of hydrogel or resin material [32,33] . The of interest, and deposited by a nozzle or needle. The
material of choice must be photosensitive. When the substrate may be a viscous liquid or a solid filament.
laser light shines onto the surface of the pool/bed of Furthermore, advances in micro-extrusion allow for
photosensitive, drug-loaded material, the material cures highly precise deposition of drug-loaded material for
[39]
and solidifies. This method is extremely high resolution small-scale products .
and considerably fast, but the nature of the pool of 3. Material Considerations
drug-loaded material has an inherent risk of cross-
contamination between the fabrications of different drug In discussing 3D printed pharmaceuticals, it is also
products. important to consider the type of material – whether it be
a powder, solid bulk, or liquefied substance – that is used
2.3 Inkjet Printing to print the drug product . SLS and binder deposition
[1]
Inkjet-based printing follows the same principles as a both require a powder substance. Compatible with
commercial inkjet printer for paper: ink is deposited onto extrusion-based printing, fused deposition modeling
a substrate by either a thermal-driven or piezoelectric- (FDM) relies on the extrusion of solid filaments loaded
driven nozzle, offering high resolution printing capa- with the desired drug. Due to the reliance on solid
bilities. With the introduction of z-axis motion, 3D polymer-based filaments, this method poses more
patterns may be fabricated by this method. challenges in making it appropriate for oral dosage
For the thermal inkjet printing approach, a thermal medicines. Conversely, natural and synthetic hydrogels
element within the print head generates droplets of have a more viscous consistency that makes them more
ink. This heating element is electrically-controlled to appropriate for oral drug products. Additionally, the

International Journal of Bioprinting (2018)–Volume 4, Issue 1 3