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6 Inkjet and Binder Jet Printing in Pharmaceuticals 229
also the most frequently used across the references cited, mostly as part of the
powder composition. Povidone is an exception, with wide use in the powder, in
the liquid, or in both input materials constructing the same final part. Mannitol and
microcrystalline cellulose also have been used frequently as part of the powder
composition over an extensive timeframe. For the printing liquid, polysorbate and
glycerin are the most common ingredients, generally to aid jetting performance and
reliability in aqueous systems.
6.5 Current Commercial Use of Binder Jetting for
Pharmaceuticals
As of this writing, Aprecia Pharmaceuticals appears to be the only entity using
binder jetting commercially for pharmaceuticals. Their website reflects services
to develop and manufacture products for partners, a full service CDMO-type
offering adaptable to partner needs for new chemical entities (NCEs) or lifecycle
management (LCM). They also generate product candidates internally, including
their first product SPRITAM. A single location serves as R&D site, commercial
manufacturing site, and corporate headquarters (Blue Ash, OH). Aprecia’s scaled
“open bed” version of binder jetting equipment (Z-Free) is used to manufacture
SPRITAM commercially from that site. In 2022, Aprecia unveiled an “in-cavity”
printing system (Z-Form Flex) that forms tablets directly within blister packages,
intended for small-scale clinical production.
In Europe, independent research organization TNO offers consulting services
across AM types in the fields of food and pharmaceuticals. Services include the
design and engineering of equipment, systems, and software, and extending to
overall process engineering and business consulting. Facilities include two additive
manufacturing laboratories. TNO offers a flexible powder bed platform for research
and material screening on binder jetting as well as selective laser sintering (TNO
Website
n.d.).
6.6 Sidebar: Inkjet Printing Without Powder
This chapter has focused on binder jetting, a form of AM that uses liquid to bind
powder. Subtract the powder component from binder jetting and what remains is a
microfluidic deposition process perhaps closer to its roots for printing on paper or
other non-particulate substrates.
When building parts entirely from jetted material, the process is considered to
be the material jetting version of AM. The absence of powder provides greater
incentive for improving the mass deposition rate of nonvolatile material through
the print head, including dose loading of drug. Accordingly, material jetting of
melts or of reactive/curable compositions becomes more desirable to minimize
the use of solvents or carrier liquids that are removed by drying. In practical
terms, melt jetting requires adequate thermal stability of drug and carrier(s) under
230 T. G. West and J. Yoo
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Tab le 6 .6 Selected examples of pharmaceutical inkjet printing without powder
Process Application Year Ref
Inkjet deposition onto
orodispersible films cast on
paper. Overcoat to modify
release.
Material jetting with
interlayer UV curing under N
inertion and subsequent
leaching of residual monomer.
Inkjet deposition onto
orodispersible films cast on
plastic sheets. Compared with
films from semisolid
extrusion.
Inline inkjet deposition onto
orodispersible film cast using
continuous coater.
Single-shot micropump
deposition (4–25 microliters)
onto compressed biconcave
tablets followed by film
overcoat and tablet marking.
Personalized oral dose in QR
code pattern linked to
embedded data.
Solid oral dosage form with
amorphous solid solution of
2
poorly soluble API.
Compounded preparations
amenable to delivery via
nasogastric tube and tracked
by QR code.
Fixed dose combination using
inkjet for one drug and film
casting for the other.
Clinical trial materials for
low-dose, high potency drugs
requiring containment (OEL
<1 microgram/m
3
8-h TWA)
2021 Chao et al. (2021)
2020 Clark et al. (2020)
2019 Öblom et al. (2019)
2018 Thabet et al. (2018)
2017 Clarke and Doughty
(2017)
conditions amenable to reliable jetting. Likewise, reactive inkjet compositions must
address chemical compatibility through the process steps as well as acceptability
of any residual unreacted material (or extraction without disturbing the dosage
form). One benefit is that these techniques do not require attention to powder
handling including separation and refeeding of unprinted powder that comprises
and surrounds binder jetted parts. Conversely, material jetting may need to form
dedicated support structures for any overhanging features until the parts harden.
As an alternative to straight material jetting, various pre-formed objects such as
compressed
tablets, edible paper, thin films, or other conventional delivery forms
may be used as receptacles for the jetted liquids as part of a multistage process.
While a full treatment of these topics is beyond the scope of the present chapter,
this
collection of nearby technology has an impressive body of work in its own right
for pharmaceutical applications. As an entry point to more substantial discussion in
this area, the reader is directed to a few recent publications listed in Table
6.6.
6.7 Future Perspectives
Even as interest in other forms of pharmaceutical Additive Manufacturing (AM)
rises, the scale-up and regulatory precedents established with pharmaceutical binder
jetting have helped shape the wider pharmaceutical AM field.
6 Inkjet and Binder Jet Printing in Pharmaceuticals 231
The coming years will likely witness increased emphasis on actualizing bestfit deployments of the technology, such as aiding early clinical trial agility for
new chemical entities, improving individualization in hospital and community
pharmacy practice, and further development of novel dosage forms for improved
drug delivery. Rare disease and orphan drug applications will remain prominent due
to a convergence of individualization with accessible scale. Additional specialized
presentations of off-patent drugs and niche line-extensions of blockbuster drugs are
also likely over time. To meet these needs, a greater variety of built-to-purpose
equipment is expected for more diverse groups of users. With sufficiently wide
adoption of the technology, new co-processed excipients might be supported specific
to certain machines and end-use scenarios.
While the first AM drug approval marked perhaps “the end of the beginning,”(W
pharmaceutical AM
and Bradbury 2019) today binder jetting is a central part of a vibrant
est
field looking to establish the best matches of capabilities to
needs across the pharmaceutical value chain.
Acknowledgments The authors wish to recognize collectively the teams from M.I.T., Therics,
and Aprecia with the origination and foundational work in pharmaceutical binder jetting, and the
broader group of researchers worldwide for increasing the study and awareness of this technology.
This dynamic interest will continue to drive the opportunities for real-world deployment of binder
jetting to help more patients today and in the years to come.
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https://
4D Printing: The Next Dimension of Healthcare
in Cancer Research
Atchara Chinnakorn, Wiwat Nuansing, Abbas Z. Kouzani,
Mahdi Bodaghi, and Ali Zolfagharian
Abstract
Four-dimensional (4D) printing has received growing interests in healthcare
with advancements in individualized dynamic constructs, including controllable
shape transformation or triggerable function upon exposure to stimuli. It is
emerging as a technology that can play a critical role in aiding cancer treatments,
with potential abilities of shape, function, or property changes, facilitating
personalized medicine for localized cancer treatments. Here, smart materials
used in 4D printed approaches are presented to explore their purpose and
utilities in aiding cancer therapeutic approaches. To guide 4D printed materials
in various perspectives, recently reported progress on applications of using 3D
and 4D printing in aiding cancer treatments and tools, such as hyperthermia,
drug delivery systems for chemotherapy, and pharmaceutical models of cancer
7
A. Chinnakorn · W. Nuansing
School of Physics, Institute of Science, Suranaree University of Technology (SUT), Nakhon
Ratchasima, Thailand
W. Nuansing (
Center of Excellent on Advanced Functional Materials (CoE-AFM), Suranaree University of
Technology, Nakhon Ratchasima, Thailand
e-mail:
A. Z. Kouzani · A. Zolfagharian ()
School of Engineering, Deakin University, Geelong, VIC, Australia
e-mail:
M. Bodaghi
Department of Engineering, School of Science and Technology, Nottingham Trent University,
Nottingham, UK
e-mail:
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
S. Banerjee (ed.), Additive Manufacturing in Pharmaceuticals,
https://doi.org/10.1007/978-981-99-2404- 2_7
)
w.nuansing@g.sut.ac.th
a.zolfagharian@deakin.edu.au
mahdi.bodaghi@ntu.ac.uk
237
238 A. Chinnakorn et al.
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
management, is discussed. Lastly, the challenges and future visions of 4D
printing research are proposed.
Keywords
4D printing · Smart materials · Cancer treatments · Drug delivery ·
Hyperthermia
Abbreviations
3D Three-dimensional
4D Four-dimensional
AAc Acrylic acid
Alg Alginate
AuNPs Gold nanoparticles
AM Additive manufacturing
AMF Alternating magnetic field
APS Ammonium persulfate
BP Black phosphorus
BPADMA Bisphenol A ethoxylate dimethacrylate
BSA Bovine serum albumin
CaP Calcium carbonate-polycaprolactone or CaCO
ChMA Methacrylamide chitosan
CMC Carboxymethyl cellulose sodium
DEX Dexamethasone
DDS Drug delivery system
DIW Direct ink writing
DoP Drop-on-powder
DOX Doxorubicin
DOX-HCL Doxorubicin hydrochloride
DPEPA Dipentaerythritol pentaacrylate
EB Egyptian blue
EMK 4,4
E-jet Electrohydrodynamic jet
F-GelMA Fish gelatin methacryloyl
Fe-DIW Femtosecond direct laser writing
FFF Fused filament fabrication
FLU or 5-FU 5-Fluorouracil
GC Gelatin-chitosan
Gel Gelatin
GelMA Gelatin methacryloyl
hIn Human insulin
IR Infrared
IS Intelligent scaffolds
LA Lauric acid
LAP Phenyl-2,4,6-trimethylbenzoyl phosphinate
L830182 Levofloxacin
MBG Mesoporous bioactive glass
MC Methylcellulose
MDA-MB-231 Human triple-negative breast cancer
Mel Melanin
-bis(diethylamino) benzophenone
-PCL
3
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