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Three-Dimensional Printing Technologies for Drug Delivery Applications
from compressed powder into male rats, achieving the use of layered cardboard contours and the photo curing of
sustained release of a testosterone API over a 2-week photo-polymer resins onto powder particles .
[2]
period . The first technique for 3D printing was developed
[4]
Since this discovery, many new methods of drug in 1951 by Otto John Munz, who detailed a method of
administration have been formulated varying from producing 3D objects through the use of surface maps
implantable devices using permeable membranes to (topoglyphs) and curing the dimensions each of these
control the release of drug, to injectable microspheres. maps into incremental layers of a vat of clear, photo-
Despite this, the majority of DDD manufacturing curable polymer resin . Since the success of this
[8]
techniques require bulk manufacturing of identical initial 3D printing technology, now widely known as
products due to high initial production costs . As a result, vat polymerization, many other methods of building
[2]
traditional DDDs fit a “one-dose-fits-all” paradigm, and up a model in a layer-by-layer approach have been
as such, between 4% and 25% of the ten top-grossing developed .
[7]
drugs in the U.S. were rendered unsuccessful in their
intended treatment , due to variances in the patients’ 2. 3D printing technologies
[5]
age, weight, medical history, and environment, among
others . In addition, many manufacturing techniques, According to the standards jointly developed by
[6]
for example, injection molding which is commonly International Organization for Standardization and
used to create implantable DDDs, often require the American Society for Standards, 3D printing technology,
heating of the polymer and API to above the polymer’s also known in a technical context as additive manufacturing
melting temperature, risking damages to the drug in the or rapid prototyping, is divided into seven categories:
process . material jetting, binder jetting, material extrusion, vat
[4]
The introduction of additively manufacturing photopolymerization, powder bed fusion (PBF), sheet
[9]
pharmaceuticals eradicates the high initial input costs lamination, and directed energy deposition . The processes
seen in traditional manufacturing techniques, opening that have been investigated for use in drug delivery
the scope for DDDs with drug doses tailored for each applications are shown in Figure 1 and are detailed in this
individual patient. In addition, the creation of parts with section. Printing techniques, printing characteristics, and
multiple materials and highly complex geometries vastly applicable materials are discussed with the aim of helping
widens the design scope of each device type to create distinguish the applicability of each process to the various
drug delivery systems with multiple release profiles . DDDs and studies detailed in section 4.
[2]
While the 3D printed drug Spritam gained U.S. Food 2.1. Inkjet printing
and Drug Administration (FDA) approval in 2016, its
potential is still largely unchartered . The following Originating from the initial concept of inkjet printing
[7]
sections in this paper detail the potential uses for 3D detailed by Lord Raleigh in 1878, traditional two-
printing in a range of pharmaceutical applications and its dimensional inkjet printing to produce documents and
current limitations. photographs was introduced by Siemens in 1951 . The
[7]
The origins of 3D printing can be split into the two deposition of droplets on top of one another to build a
sub-fields of photo sculpture and topography: 3D part was later developed in the 1980s. Inkjet printing
can be split into two classifications: material jetting and
1.1. Photo sculpture binder jetting .
[7]
In the 1800s, the process of using multiple photographs
from differing angles of a 3D object was introduced. (1) Material jetting (MJ)
These early technologies required the artist to carve the MJ can be defined as the process in which droplets
photographed silhouettes of each object or person from of build material are selectively deposited onto a
each angle to create a completed 3D sculpture . In the substrate and can be split into two main techniques:
[3]
[9]
1900s, Carlo Baese patented a simplified technique, drop on demand (DoD) and continuous inkjet (CIJ)
implementing light to a photo-sensitive gelatine to create (Figure 2) [7,10] .
a replica of the original model . DoD technique includes the use of either a vapor
[8]
bubble or piezoelectric crystal which are subject to an
1.2. Topography increase in heat or voltage, respectively, to enlarge and
The concept of combining multiple layers with differing force the ink from the nozzle, following which the input
geometries was suggested by Blanther in the 1890s, force is removed, allowing the nozzle to refill. In contrast,
who layered wax sections on top of one another and CIJ technique charge droplets upon ejection, following
smoothed them together to make a 3D structure . which deflector plates deflect them either onto the
[8]
Numerous variations of this concept ensued, such as the substrate or away as waste to be recirculated (Table 1) [7,10] .
322 International Journal of Bioprinting (2022)–Volume 8, Issue 4