The document discusses three-dimensional printing (3D printing) technology, highlighting its transformative potential in various fields, especially healthcare, due to recent FDA approvals and advancements. It covers different 3D printing methods, including SLA, DLP, and FDM, and their applications in rapid prototyping, personalized medicine, and drug delivery. The benefits of 3D printing include cost efficiency, customization, complex fabrication capabilities, and innovative dosage forms, which are set to revolutionize the pharmaceutical industry.

1. PRESENTED BY: LAD HEALY GUNVANT
GUIDED BY: DR. RAJASHREE MASHRU MA'AM

2.  Three dimensional printing (3DP) technology is a new
strategy for rapid-fire prototyping, which constructs solid
objects by deposit of several layers in sequence.
 The preface and operation of 3D printing have promoted
enormous inventions in numerous different fields,
including aerospace diligence, framework, tissue
mastermind, biomedical investigation and drugstore.
 The recent preface of the first FDA approved 3D- printed
medicine has fuelled interest in 3D printing technology,
which is set to transform healthcare.
 Generally, the polymer systems has always attained the
attention of manufacturers due to their unique
characteristics similar as ease of processing, light
weight, low cost, long life, and frequently rigidity.
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►Facilitate rapid-fire prototyping (e.g., elimination of tooling engineering of molds, dies, or
institutions).
►Enhance design rigidity and fabrication customizability (e.g., cells, configurations, froths, etc).
►Enable complex configuration and dimensions (e.g., topologies, substructures and undercuts).
►Tune localized chemical compositions (e.g., multi-materials, biomaterials, functional grading).
►Knitter physical morphologies (e.g., the exposure of constitute structure blocks).
►Waste zero or limited materials (e.g., no machining required and high recyclability of feedstocks).

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1. TYPES OF POLYMERS &
NANOPARTICLES
2. DISPERSION OF
NANOPARTICLES
3. INTERFACIAL INTERACTION
4. ORIENTATION OR ALIGNMENT
OF PARTICLES OR POLYMER
CHAIN

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1. PHOTOCURING BASED PROCESS
 SLA based printing
 2PP/MPP based printing
 DLP based printing
2. JETTING BASED PROCESS
 Inkjet based printing
 EHD based printing
 Binder Jet based printing
3. EXTRUSION BASED PROCESS
 FDM based printing
 LDM based printing
 PBF based printing
METHODS
PHOTOCURING
JETTING
EXTRUSION

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► SLA(Stereolithography) is form of 3D printing technology as a
vat photopolymerization process used to produce parts from
photopolymer materials in a liquid state using one or further lasers
to widely cure to a predestined consistency and harden the
material into shape layer upon layer.
► Microcapsules filled with healing fluids synthesized using in situ
interfacial polymerizations were dispersed in marketable resin
before SLA 3D printing self- healing compound samples; the
microcapsules survived the SLA process and fluid was released
during mending procedures. SLA- published structures have
advantages in biomedical usages.
► As a result, optimizing the interfacial relations combined with
the SLA- enabled, gradually ordered biomaterials has displayed
accommodated biological and medical functionalities.
► Still, the preface of underpinning fillings can cause problems,
similar as increased density, scattering of UV light, and
overheating of localized regions. The increased density
will reduce down processing.
1. SLA BASED PRINTING:

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►UVlight scattering reduces UV penetration depth and side resolution, preventing a more
comprehensive irradiation energy source, an advanced laser power, or UV-transparent
underpinning fillings.
►The localized overheating may cause pre-mature curing or prematurely- stage polymer
degradation.
►Additives distributed in the resin/ particle system can ease polymerization, modify density,
stabilize the particle suspensions, or enhance interfacial adhesion.
► A many particles have known underpinning effects in polymers for Young’s modulus, tensile and
flexural strength, and durability.

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1. one-photon polymerization(1 PP): An generator in a
photopolymerization vat ( i.e., photoresist) substantially
composed of monomers or oligomers absorbs one UV photon
with a short wavelength through a linear absorption to initiate
polymer chain growth. Due to low penetration effectiveness,
the photoresist absorbs UV light only within the first few
micrometers and provides the same microns’ resolution.
2. two-photon polymerization(2 PP): It is effectively confined to
the narrow focal volume or point of the laser (e.g., 60 nm in
three range), which is much lower than the diffraction limit of
the excitation laser wavelength (e.g., 780 – 800 nm
polymerization (MPP) has a simultaneous absorption of three
or further photons during polymer photocrosslinking.
Two-photon or multiphoton
approaches, also known as Direct
Laser Writing (DLW) and first
introduced in monomer
polymerizations, have been helpful in
tissue engineering and drug delivery
due to their important fabrication
capability for building precise
microstructures with high spatial
resolution on both the microscopic
and nanometric scale.

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►Utmost photo curable resins are free-radical or cationic
photoresponsive and display high brittleness upon curing. It was
developed high- performance elastomeric materials to overcome
the high crosslinked structure and printed object fragility. During
amalgamated preparation, a type of branched mercaptan-
functionalized polysiloxane was synthesized and compounded with
different-molecular- weight vinyl- terminated poly
(dimethylsiloxane) (PDMS). Different contents of underpinning
fillings (e.g., particles of fused silica and precipitated silica at a
concentration of 5 wt-20 wt), photoresists, and photoinitiators
showed tunable mechanical properties and adaptability for
silicone/ silica admixtures.
►Thus improved materials with super stretchability, high
biocompatibility, and low cytotoxicity are advantageous for soft
robots and biomedical devices. Silicone can serve as a preceramic
polymer resin. Thus, silicone’s fast solidification in DLP can rapidly
prototype complex structures, similar as porous,
cellular, and layered structures.
► DLP(Digital Light Processing)
is a 3D printing technology
which used to rapidly produced
photopolymers parts. It is very
similar to SLA the only
diiference is DLP uses projected
light source to cure the entire
layer at once

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►Each deposited layer must be cured in between successive
depositions, and the curing process will vary depending on the
materials used to print your product. Inkjet 3D printing systems
include equipment for curing each layer within the system.
►inkjet printing is complexity agnostic, meaning the printing time is
nearly independent of product complexity. The time required to print a
fully functional product depends solely on the time required to deposit
the necessary amount of material and the curing time.
►As a result, the cost structure only depends on the weight of the
material being deposited and the energy consumed during
deposition—costs in both of these areas are fixed. When printing
complex multilayer and non-planar PCBs, all interconnects,
mounting holes, and vias can be printed directly without additional
machining steps.This reducesthe total manufacturing time from
weeks to hours with a highly predictable cost structure.
1. INKJET BASED PRINTING
► 3D inkjet printing is a low-
temperature, low-pressure process
that involves the deposition of liquid
materials or solid suspensions.
Polymers, dielectric nanoparticles,
and conductive nanoparticles can
be deposited with this process,
making it adaptable to a broad range
of materials. In this process, the
printing material is extruded through
a small nozzle within a print head. As
the print head raster scans over a
surface, multiple layers are built up in
a layer-by-layer process.

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►General principles should be followed for using the EHD jet.
1. First, the EHD printhead radius should be small. Different
organic, inorganic, or metallic particles are useable, and
needle size should be larger than the particle size.
2. Second, the electrical field strength and the inflow rates
should match so that droplets formed are cone- jet or micro-
dripping. The actuation principle from the electrical voltage
pulse allows the conformation of droplets as small as tens of
nanometers.
3. Third, the electrical field strength is tunable for drop deposit
range that generally increases with a high electrical field. For
illustration, the printing line range can range from 1 to 10 μm
during 700 – 1000V.
4. Finally, the stage moving rates on the EHD platform can
determine the printing line morphology (coiled or
continuous) and the fiber radius.
►Electrohydrodynamic jet (e-jet)
printing is a high resolution
printing technology where the
printed liquid is driven by an
electric field. Exposure to an
electric field causes mobile ions
in a polarizable liquid to
accumulate at the liquid surface.

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►Binder jetting, also named drop-on- bed (DOB), jets liquid binders through an inkjet printer head on
spread powders and widely combines them into a patterned layer with x/ y direction. Ideal binders have
proper rheology, sufficient wettability, stable chemistry, and effective binding strength.
►The binder inks impact the polymer powder with small picoliter drop. The impact speed is on the scale
of meters/ s. A high impact speed will increase production rates but will also increase impact radius and
reduces spatial resolution.
►There's a balance between drop spreading and infiltration depth, with the former controlled by surface
tension and the ultimate driven by capillary effects.
►The primary advantages of binder jetting include:
I. high friendliness to a broader range of materials than selective laser sintering,
II. room temperature admixture that avoids polymer oxidation or degradation,
III. no support structures required as in FDM
IV. Better control of material viscosity by simply tuning heating temperatures for void coalescence.

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FDM-BASED PRINTING:
► Fused Deposition Modeling (FDM) Technology works with specialized 3D printers and production-
grade thermoplastics to build strong, durable and dimensionally stable parts with the best accuracy
and repeatability of any 3D printing technology.
► FDM 3D Printing, is a method of additive manufacturing where layers of materials are fused together
in a pattern to create an object. The material is usually melted just past its glass transition
temperature, and then extruded in a pattern next to or on top of previous extrusions, creating an
object layer by layer.
► Fused deposition modeling (FDM), a type of 3D printing technology, is the most quoted when dealing
with production of drug delivery devices, because of the low cost of printers; printing precision,
fundamental to guaranteeing medicine quality parameters; and hot-melt extrusion, a technological
process incorporated in the pharmaceutical field.
► uses heat to melt a polymeric filament and deposit it layer by layer in the x, y and z-axes, creating a
three-dimensional product.The filament used to feed the printer is produced by hot-melt extrusion
using active pharmaceutical ingredients and pharmaceutical grade polymers

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►There are three ways to print particle- included polymer mixes:
I. Integrate liquid resin and in-situ polymerization before extrusion (e.g., anterior polymerization);
II. Fuse molten thermoplastic on moving nonstop filaments (e.g., CF) with core- shell fibers;
III. Extrude pre-impregnated paddings with polymer coatings.

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►Enhanced productivity: 3D printing works more quickly in contrast to traditional methods especially
when it comes to fabrication of items like prosthetics and implants with an additional benefit of better
resolution, repeatability, more accuracy, and reliability
►Customization and personalization: One of the pioneer benefits of this technology is the liberty of
fabrication of customized medical equipment and products. Customized implants, prosthetics, surgical
tools, fixtures can be a great boon to patients as well as physicians
►Increased cost efficiency: Objects produced by 3D printing are of low cost. It is an advantage for
small-scale production units or for companies that produce highly complex products or parts because
almost all ingredients are inexpensive.By eradicating the use of unnecessary resources, manufacturing
cost can also be reduced. For instance, 20-mg tablets could be potentially formulated as 1-mg tablets
as per need.
►3DP allows controlled size of droplets, complex drug release profiles, strength of dosage and multi-
dosing

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►Unique dosage forms: infinite dosage forms can be created using 3D printing. Inkjet-based 3D printing
and inkjet powder-based 3D printing are the two main printing technologies employed in the
pharmaceutical industry. Microcapusles, antiobiotic printed micropatterns, mesoporous bioactive glass
scaffolds, nanosuspensions, and hyaluronan-based synthetic extracellular matrices are some of the
novel dosage forms formulated using 3D printing.
►Personalized drug dosing: Drugs with narrow therapeutic index can easily be prepared using 3D
printing; and, by knowing the patient’s pharmacogenetic profile and other characteristics like age, race
etc., optimal dosage can be given to the patient. Preparation of entirely new formulation is another vital
potential of 3D printing for instance fabrications of pills that have a blend of more than one active
pharmaceutical ingredient or dispensed as multi-reservoir printed tablets. Hence patients suffering from
more than one disease can get their formulation ready in one multi-dose form at the healthcare point
itself, thereby providing personalized and accurate dose to the patient with better or best compliance.

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►Complex drug release profile: In most conventional compressed dosage forms, a simple drug release
profile which is a homogenous mixture of active ingredients is observed. Whereas in 3D printed dosage
forms, a complex drug release profile that allows fabrication of complex geometries that are porous and
loaded with multiple drugs throughout, surrounded by barrier layers that modulate release, is found.
►One example is the printing of a multilayered bone implant with a distinct drug release profile alternating
between rifampicin and isoniazid in a pulse release mechanism. 3D printing has also been used to print
antibiotic micropatterns on paper, which have been used as drug implants to eradicate Staphylococcus
epidermidis.

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►3D printing technology is a valuable and potential tool for the pharmaceutical sector, leading to
personalized medicine focused on the patients’ needs. It offers numerous advantages, such as
increasing the cost efficiency and the manufacturing speed. 3D printing has revolutionized the way in
which manufacturing is done. It improves the design manufacturing and reduces lead time and tooling
cost for new products. This chapter has summarized different fabrication methods and some notable
applications of 3D printing in the healthcare sector, especially in pharmaceutical sciences.

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► 3D printing for polymer/particle-based processing: Weiheng Xu a,1, Sayli Jambhulkar a,1, Yuxiang Zhu a, Dharneedar
Ravichandran a, Mounika Kakarla b, Brent Vernon c, David G. Lott d, Jeffrey L. Cornella e, Orit Shefi f, Guillaume
Miquelard-Garnier g, Yang Yang h, Kenan Song
►
► R. Durga Prasad Reddy, V. Sharma, Additive manufacturing in drug delivery applications: a review, Int. J. Pharm. 589
(2020) 119820.
► A.J. Capel, R.P. Rimington, M.P. Lewis, S.D.R. Christie, 3D printing for chemical, pharmaceutical and biological
applications, Nat. Rev. Chem. 2 (12) (2018) 422–436.
► G. Chen, Y. Xu, P. Chi Lip Kwok, L. Kang, Pharmaceutical applications of 3D printing, Addit. Manufact. 34 (2020)
101209.
► ASTM, Standard Terminology for Additive Manufacturing Technologies, F2792 12a, 2012.
► S. Infanger, A. Haemmerli, S. Iliev, A. Baier, E. Stoyanov, J. Quodbach, Powder bed 3D-printing of highly loaded drug
delivery devices with hydroxypropyl cellulose as solid binder, Int. J. Pharm. 555 (2019) 198–206

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