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Three-Dimensional Printing Technologies for Drug Delivery Applications
Binder jetting has since been investigated to print a
range of dissolution profiles, including those exhibiting
zero-order release, fast-dissolving tablets, and extended
release in addition to fast-disintegrating oral films, which
led to the first 3D printed drug Spritam that showed drug
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release within the therapeutic window within 9 min of
administration being given approval by the U.S. FDA in
2016 for the treatment of epilepsy .
[35]
BJ of ODDDs usually includes the drug in the
polymer powder. Unlike BJ process, the API is situated in
the injectable ink for MJ printing and solidified by either
polymer cross-linking or solvent evaporation, so fewer
studies have been conducted using this inkjet method. The
first use of MJ in pharmaceutical printing was by Hsu et al.
in 2015 who printed multi-layer tablets using naproxen
(NAP)/polyethylene glycol (PEG) solid dispersions with
various PEG barriers to control the release rate of the NAP,
with higher dissolution rates being evident with the increasing
PEG molecular weight . Later studies investigated the
[36]
effect of geometry on drug release, and Kyobula et al.
Figure 6. Examples of drug delivery devices.
detailed faster release rates with higher surface areas, with
the highlighted limitation being the factor of wettability of
administration, regularly exhibiting near-immediate the inner honeycomb structure of smaller cell sizes .
[37]
release profiles . Extrusion-based 3D printing techniques have also
[32]
Modern ODDDs can be designed to exhibit a range been explored to manufacture ODDDs with tuneable release
of release speeds and manufactured with multiple drugs. profiles. Filament extrusion has been used to print a range of
Despite this, traditional powder compaction methods immediate, extended and modified release profiles through
largely restrict the design freedom and therefore hinder the the use of polymers include poly (lactic acid) (PLA), poly
therapeutic efficacy of the dosage form. In addition, the (vinyl alcohol) (PVA), PEG, and its diacrylates (PEGDA).
high initial investment costs for the compression mold and Although a range of biodegradable and biocompatible
high input energy requires the production of large volumes materials are able to extrude filament, the generally high
of pills per cycle to reduce processing costs . As such, molecular weights required to retain its form upon printing
[12]
tablet variance is not possible and results in all produced tend to correlate to slow degradation rates; to deal with
pills falling under the “one-dose-fits-all” paradigm. Other this, a number of studies have been explored. Alhijjaj et al.
problems include the even dispersion of the API within the performed an investigation into the blending of multiple
polymer excipient, and therefore in the pills, along with the polymers to widen the material base for extrusion-printing
restriction on producing pills with multiple drugs due to in pharmaceutics, and to control drug release rate through
the potential of interactions between the differing drugs . the polymer blend . Arafat et al. incorporated “caplets”
[32]
[38]
Printing of ODDDs was first investigated into into the print, thereby achieving faster degradation rates
a 3D part in 1999, when Kastra et al. began to use due to an increase in fluid flow throughout the pill , and
[39]
binder jetting to tailor release mechanisms via the use Sadia et al. included perforating channels , whereas
[40]
of different binder inks. Binder inks containing either Goyanes et al. created similar pores in the pill structure
Eudragit E-100 with ethanol or Eudragit RLPO onto by reducing the % infill of the pill in the printing process
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cellulose powder to produce tablets exhibiting either while investigating the effect of external geometry on drug
erosion or diffusion-based drug release. In addition, the release, and concluded that an increase in surface area/
ability to tailor the release profile by varying of quantity volume ratio corresponds to an increase in release rate .
[41]
of polymer in the ink was demonstrated, with lower Alternatively, Goyanes et al. investigated the filament
polymer concentrations exhibiting faster dissolution extrusion printing of caplets to achieve a fast pulse of drug
rates . In their further studies, Rowe et al. utilized the release upon the dissolution of the outer shell . To achieve
[33]
[42]
pH dependency of excipients to control drug release in sustained release, filament extrusion has been shown to
correlation to the ingested ODDDs location in the body, print tablets with hollow or lattice internal structures in
and achieved immediate release, DR, break-away devices order to keep the ingested pills within the stomach for a
capable of exhibiting two pulses of drug release through sustained period [43,44] . 3D printing technologies for oral drug
the incorporation of multiple material and drugs . dosage form are shown in Table 9.
[34]
330 International Journal of Bioprinting (2022)–Volume 8, Issue 4