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ABSTRACT

The pharmaceutical industry is moving ahead at a rapid pace. Modern technology

has enabled the development of novel dosage forms for targeted therapy. However,
the fabrication of novel dosage forms at industrial scale is limited and the industry
still runs on conventional drug delivery systems, especially modified tablets. The
introduction of 3D printing technology in the pharmaceutical industry has opened
new horizons in the research and development of printed materials and devices.
The main benefits of 3D printing technology lie in the production of small batches
of medicines, each with tailored dosages, shapes, sizes, and release characteristics.
The manufacture of medicines in this way may finally lead to the concept of
personalized medicines becoming a reality. This chapter provides an overview of
how 3D printed technology has extended from initial unit operations to developed
final products.
The 3D PRINTING technology has caught the attention of medical devices
industry and pharmaceutical industry due to its applications on various
platform in health care industry. Even though this technology exists for a long time
it is of public interest highly now due to the approval of 3-D printed tablet and
other medical devices and also with the advent of USFDA’s guidance on technical
considerations specific to devices using additive manufacturing which
encompasses 3-dimensional (3D) printing has triggered many thoughts about this
technology which needs to be considered for successful delivery of intended
product. This paper presents regulatory agencies expectations, limitations,
problems in establishing such setups for production of drug products, advantages,
disadvantages, applications, methods and associated risks involved in
manufacturing. It also provides the comprehensive review of the current status of
research and development on this platform

Keywords: 3D print, personalized medicines, manufacturing, drug delivery

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INTRODUCTION TO 3D PRINTING

Gaining immense interest both in academic and industrial sector is the concept of
three dimensional (3D) printing (3DP) technologies. Domains like aerospace,
engineering, FMCG, architecture, military, fashion industry, chemical industry,
and medical field are by no way untouched by this technology. 3DP has a wide
range of applications like tissue design, printing of organ, diagnostics, manufacture
of biomedical devices, and the design of drug and delivery systems in the medical
field. From the data originated by various techniques like computed tomography
(CT) scan and magnetic resonance imaging (MRI), complex anatomical and
medical structures according to the need of patient can be fabricated. Replacing
and repairing the defective organs like kidney, heart etc. or all together creating a
new organ that mimics the same functions as that of original are some additional
uses of this technology. This technology is so widespread that its applications
include things that are an integral part of human life like clothing, eyeglasses,
jewelry, parts of cars, and drugs that can be printed in almost any geometry and
shape as per the requirement of the user. In this technology a concept is
transformed into prototype by taking help from 3D computer-aided design (CAD)
files, hence digitally controlled and customized product can be fabricated. This
technology utilizes a bottom-up approach in which layers of materials like living
cells, wood, alloy, thermoplastic, metals etc. are placed on top of each other in
order to make the required 3D object. Therefore, 3D printing is also known by
other terminologies such as layered manufacturing, additive manufacturing,
computer automated manufacturing, rapid prototyping, or solid freeform
technology (SFF). Pharmaceutical Formulation Design - Recent Practices 2 In
subtractive methodology or conventional method, the product is designed from the
bulk substance and due to non-advanced tools used non-standard geometries and
objects made from many materials cannot be made with high quality. In contrast to
the conventional method, 3DP technology is more automated, rapid and easy to
use, customized and sophisticated and cost-effective.
Drug delivery is the technology and formulation developed to efficiently transport
a pharmacologically active compound in the body to achieve Therapeutic
efficiency in a safe manner. The efficiency and safety of a pharmaceutical product
can be improved by controlling the release profile which in turn modulates the
pharmacokinetics of a drug. The inter-species variability is an obstacle
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frequently faced in the clinical scenario. Customized medicine and dosing

receives increasing attention because of the high chances of undesirable side
effects. The probability of adverse reactions is higher in the pediatric and
geriatric populations when the bulk manufacturing of pharmaceuticals
concentrates on the average population.
3D printing can play a significant role in multiple active ingredient dosage forms,
where the formulation can be as a single blend or multi layer printed tablets
with sustained release properties. This reduces the frequency and number of
dosage form units consumed by the patient on a daily routine. 3D printing
technology has high potential in individualized dosage form concept called
the polypill concept. This brings about the possibility of all the drugs required
for the therapy into a single dosage form unit.Three dimensional printing
technology is a novel rapid prototyping technique in which solid objects are
constructed by depositing several layers in sequence.
The rapid prototyping involves the construction of physical models using
computer-aided design in three dimension. It is also known as additive
manufacturing and solid free form fabrication. 3D printing Technology has
enabled unprecedented flexibility in the design and manufacturing of complex
objects, which can be utilized in personalized and programmable medicine.
It is an effective strategy to overcome some challenges of conventional
pharmaceutical unit operations.
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HISTORY

3D Printing posed as a possible platform for personalized medicine in the

1990s. There are major achievements in 3D printed medical device, FDA’s
Center for Device and Radiological Health (CDRH) has reviewed and cleared 3DP
medical devices.The first 3D printing technique used in pharmaceutics was
achieved by inkjet printing a binder solution onto a powder bed, binding therefore
the particles together. The process was repeated until the final desired structure
was obtained. This first happened in the early 90’s at the Massachuset
Institute Technology invented and patented by Sachs et al.
In 1989, Scott Crump, filed a patent on another 3D printing technology:
fused deposition modeling, where extruded polymer filaments heated into a
semi-liquid state were extruded through a heated nozzle and deposited onto a
build platform layer by layer to harden. Inkjet printing was the method used to
manufacture Spritam (levetiracetam) tablets for oral use, the first 3D printed drug
approved by the Food and Drug Administration (FDA) in 2016 by Aprecia
Pharmaceuticals.
3D printing is more advanced in the fields of automobile, aerospace,
biomedical and tissue engineering than in the pharmaceutical industry where it
is in its initial phase. FDA encourages the development of advanced manufacturing
technologies, including 3D-printing, using risk-based approaches.

Regulatory Expectations

US FDA, 2017 issued guidance on Technical

Considerations for Additive Manufactured Medical Devices, this guidance
outlines various requirements, like Design and Manufacturing Process
Considerations, Device Testing Considerations and labeling. It also suggests
the validation of the processes involved to provide high degree of assurance
according to the established procedures.
In addition documentation must be done to conform to the existing guidelines
in the Quality System regulation for device validation. Process validation must
be performed to ensure and maintain quality for all devices and components
built in a single build cycle, between build cycles, and between machines,
where the results of a process (i.e., output specifications) cannot be fully
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verified by subsequent inspection and test. Software also must be validated for its
intended use according to an established protocol. The following examples Were
suggested in the guidance with respect to powder bed fusion technologies,
 In-process monitoring of parameters such as: temperature at the beam focus,
melt pool data,
 Build-space environmental conditions (e.g., temperature, pressure, humidity),
 Power of the energy delivery system (e.g., laser,electron beam, extruder),
 Status of mechanical elements of the printing system (e.g., recoater, gantry)
 Manual or automated visual inspection with defined acceptance criteria,
 Non-destructive evaluation, and
 Test coupon evaluation
Changes to the device, manufacturing process, or process deviations should be
identified and analyzed for the potential risks they introduce. Based on this
assessment, the change or deviation may trigger the need for revalidation of the
process. Manufacturers should rely on existing FDA Guidance for their
regulatory pathway when considering a change to a previously cleared or
approved device that uses additive manufacturing. Some examples of triggers
for revalidation specific to additive manufacturing are:
 Software changes (e.g., change or update of build preparation software),
 Changes in material (e.g., supplier, incoming material specification, reused
powder, new formulation) or material handling,
 Change in the spacing or orientation of devices or components in the build
volume,
 Changes to the software workflow,
 Physically moving the machine to a new location, and
 Changes to post-processing steps or parameters
The distinction between compounded and manufactured medicine is a central
question about the regulations of 3D printed medicine. Tragic incidents such as
the New England Compounding Centre (NECC) in 2012 and dozens of other
dangerous safety problems at compounding pharmacies, have put the safety
of pharmaceuticals under the spotlight. Like manufacturing of dosage forms, a
3D printed drug product have to be manufactured by following the
established regulations for manufacturing of drug products meeting the current
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chemistry, manufacturing and control (CMC) standards provided in the 21 CFR

200 & 300 and other applicable guidance.
Important issues concerning 3D printed medicines like tort liability and
intellectual rights need to be addressed to protect manufacturers and end users.
Meeting current regulatory requirements of the FDA may pose a significant
hurdle that can impede their introduction to the market. FDA may need to issue
short term guidance documents and look into modifying its traditional regulations
to follow up with this rapidly-evolving technology. Two laboratories within the
FDA’s Office of Science and Engineering Laboratories (OSEL), the Laboratory
for Solid Mechanics and FDA’s Functional Performance and Device Use
Laboratory are being utilized for the purpose of studying the potential effects of
3D printing.
In spite of all regulatory hurdles associated with 3D printing medicine, the
FDA approved the first 3D printed pill, Spritam® (levetiracetam) in August
2015.
In this case the product is considered as approving new mass production for
equivalent product.
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STEPS INVOLVED IN A 3D PRINTED DOSAGE FORM

Pharmaceutical product is designed in three dimension with computer aided design

Design is converted to a machine readable format which describes the external
surface of the 3D dosage form.
The computer program then slices this surface into several distinct printable
layers and transfers that layer-by-layer to the machine.

Advantages of A 3d Printed Drug Delivery:

 High drug loading ability when compared to conventional dosage forms
 Accurate and precise dosing of potent drugs which are administered at small
doses
 Reduces cost of production due to lesser material wastage
 Suitable drug delivery for difficult to formulate active ingredients like poor
water solubility, drugs with narrow therapeutic window
 Medication can be tailored to a patient in particular based on genetic variations,
ethnic differences, age, gender and environment.
 In case of multi drug therapy with multiple dosing regimen, treatment can be
customized to improve patient adherence.
 As immediate and controlled release layers can be incorporated due to the
flexible design and manufacture of this dosage form, it helps in choosing the
best therapeutic regime for an individual.
 Avoids batch-to-batch variations seen in bulk manufacturing of conventional
dosage forms.
 3D printers occupy minimal space and are affordable.
 Manufacture of small batch is feasible and the process can be completed in a
single run.
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Integration of Personalized Medicine with Healthcare Network

As 3D printers perform as computerized fabricators that manufacture 3D objects
based on command generated by computer software, it has an immense
possibility of integrating the 3D printers with the healthcare network.
This concept uses sensor technology which will enable sensors to be placed on
patients. These sensors generate clinical data feed that eventually gets stored in
healthcare network. The healthcare professional can manufacture the next
dose according to the patient’s physiological changes reflected in the clinical
data transmitted. Hence, such a dispensing system offers a clear advantage of
shortening the time of a clinical response to patient’s needs and improving
patient’s compliance.
To incorporate the practical application of 3D printed dosage form into the
dispensing scenario existing today, further research and development in the clinical
scenario is essential. First of all, the software technology used can be further
optimized and improved. Secondly, excipients need to be developed for
optimum application in 3D formulations. Thirdly, manufacturing process has to
be developed and optimized for a wide range of drug products. Fourthly
efficacy, safety and stability of new 3D-based formulations have to be studied
further because the built in flexibility should not become a liability on safety.
The principle employed in 3D printing drug delivery systems is the
construction and stacking of layers of 3D printed objects. The name of the
technology is usually related to the technique involved in layer formation. 3D
printing is repeated and co-ordinated two-dimensional printing.

Spritam® - Fda Approved First 3d Printed Pill

SPRITAM utilizes Aprecia’s proprietary ZipDose® Technology platform, a
groundbreaking advance that uses three-dimensional printing to produce a
porous formulation that rapidly disintegrates with a sip of liquid
ZipDose technology enables the delivery of a high drug load, up to 1,000 mg in
a single dose. SPRITAM enhances the patient experience - administration of
even the largest strengths of levetiracetam with just a sip of liquid. Aprecia
developed its ZipDose Technology platform using the 3DP technology that
originated at Massachusetts Institute of Technology.
The ZipDose technique is based on layer-by-layer powder bed fusion system.
The first layer consists of the active pharmaceutical ingredient and excipients
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required for the matrix tablet. Subsequently, a binder liquid is deposited for
perfect integration and aggregation between all of the successive and identical
layers.

Polypill concept
The concept of “polypill” refers to a single tablet that includes the
combination of several drugs.This concept is highly beneficial for geriatric
population, as patients of this age category are prone to multiple disorders and
hence multiple therapy.
The technology has been realized through the research of Khalid et al, where
five different active pharmaceutical ingredients with different release profiles
have been formulated in a single 3D dosage form. Three drugs (pravastatin,
atenolol, and ramipril) were printed in the extended release compartment. The
drugs were physically separated by a permeable membrane of hydrophobic
cellulose acetate. An immediate release compartment containing aspirin and
hydrochlorothiazide was deposited on top of the extended release
compartment.

three-dimensional (3D) extrusion-based printing was used to manufacture the

'polypill' to demonstrate that complex medication regimes can be combined in a
single tablet and that it is viable to formulate and 'dial up' this single tablet for the
particular needs of an individual. The tablets used to illustrate this concept
incorporate an osmotic pump with the drug captopril and sustained release
compartments with the drugs nifedipine and glipizide. This combination of
medicines could potentially be used to treat diabetics suffering from hypertension.
The room temperature extrusion process used to print the formulations used
excipients commonly employed in the pharmaceutical industry.
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Types of 3D printing technology

Fused deposition modeling (FDM)

The process involves the selection of the desired polymer, which is melted and
forced through a movable heated nozzle. Along the entire 3 axis (i.e., x-y-z), the
polymer is laid down layer by layer, which on solidification gives the exact shape
as was designed by computer aided design models. Multiple dosage forms like
implants, zero-order release tablets etc. that include polymer as a part of their
formulation can be made by this method.

Inkjet Printing
This approach to personalized medicine originates from the same technique of
computer-operated inkjet printing. It was adapted for pharmaceutical application
by the replacement of the ink with pharmaceutical solutions containing drugs and
normal paper with edible sheets known as substrates.
Dose alterations are done by altering the number of layers printed in a given area
or changing the area to be printed. The drug and excipients are design in a ratio
such that it has a potential to print as microdots onto an edible substrate. The two
main printing types employed under inkjet printing are thermal inkjet printers and
piezoelectric inkjet printers.
Printing-based inkjet systems encompass two types of techniques: continuous
inkjet printing (CIJ) and dropon-demand (DOD) printing. In continuous inkjet
printing, the liquid ink is directed through an orifice of 50-80 µm diameter creating
a continuous ink flow. The liquid is caused to flow and break into drops at a
specified speed and size at regular intervals using a piezoelectric crystal. These
parameters are controlled by creating an electrostatic field. Thus, the droplets are
charged and separated by “droplets of guard” to minimize the electrostatic
repulsion between them. The electrostatic field created directs the charged droplets
to the substrate.
The drop-on-demand technique contains multiple heads (100–1000) and can use
two types of translators, a thermal head or a piezoelectric crystal. The thermal head
is restricted only to volatile liquids, whereas the piezoelectric covers a wide range
of liquids. In addition, the thermal head reaches temperatures of up to 300 ºC,
which implies that the use of solvents of high vapor pressure could cause the
degradation of bioactive compounds. This factor limits the use of thermal print
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heads for pharmaceutical applications [andrea]. The piezoelectric crystal changes

rapidly, but this can generate a sudden variation of volume. Both of the heads are
capable of producing droplets of between 10 and 50 µm, corresponding to a
volume of between 1 to 70 pL. The ability to operate at room temperature, with
less volatile and more biocompatible liquids, makes piezoelectric printing
technology more suitable for the development of drug delivery devices.
The DOD technique has 2 subtypes: drop-on-drop deposition and drop-on-solid
deposition (powder bed fusion). Inkjet drug printing offers a significant advantage
of accurate control of dose combination and pattern of drug release. Ink jet printing
requires the starting materials to possess certain characteristics mainly; particle
size needs to be < 20 cP and surface tension between 30 and 70 mN/m for efficient
flow.
This makes inkjet printing suitable for drugs with very low therapeutic doses.
Formulating higher doses through this technology poses difficulty in the form of
longer drying time for multiple layer printing on a particular area. Increasing
surface area to sort this problem would in turn increase the size of the dosage form.

Laser-Based Writing System

It is based on the principle of photopolymerization, in which free radicals are
released after the interaction between the photoinitiator and UV light

Stereolithographic 3D Printing
This technique involves the curing of photosensitive material/s (photo-
polymerization) to produces a 3D object. Scanning a focused Ultraviolet (UV)
laser over the top of a photopolymerizable liquid in a layer by layer fashion, SLA
employs a digital mirroring device to initiate a chemical reaction in the
photopolymer which causes the gelation of the exposed area. This process is
repeated layer after layer to build the entire parts of the object. This occurs as
unreacted functional groups on the solidified structure in the first layer polymerises
with the illuminated resin in the next layer ensuring adhesion and Ani Jose.et al
Asian Journal of Pharmaceutical and Development. therefore, layer formation. Post
printing processing is usually required to further cure the final product, to improve
its mechanical integrity and to polish or remove the attached supports to the
fabricated object. This technique however possesses a health hazard in the form of
potential carcinogenic resins. This is also a very slow process. SLA printers are
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composed of an ultraviolet light beam, in the form of a laser, which transfers the
energy into a liquid photopolymerizable resin. The ultraviolet light beam is aided
by baffles, axes x and y, to traverse the surface of the liquid resin, in order
tovaccurately represent the 3D model, previously designed. When a layer
solidifies, the lifting platform descends its position to the height of a new layer of
liquid resin, again beginning the procedure, until the manufacture of the 3D
product is finished in a layer-by-layer way. Here thickness of the cured layers
depends upon the energy of the UV light to which resin is exposed. The resin
should be FDA approved for human use with the ability to solidify upon exposure
to laser beam.

Selective Laser Sintering 3D Printing

This technique also involves powder bed being spread as thin layers and utilizes
laser radiations to liquefy and fuse the powder layers (34). This is a lesser used
method due to the possibility of chemical degradation (4). A laser beam sinters the
powder and binds it in layer-bylayer fashion

.
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3D printing procedure

First, a virtual 3D design of an object using digital design software like Onshape,
Solidworks, Creo parametric, Autocad, Autodesk etc. is created

This digital model is then converted to (.STL) digital file format which stands for
standard tessallation language or stereolithography

Triangulated facets give information regarding the surface of the 3D model that is
present in the (.STL) file.

The (.STL) file is converted into G file by slicing the design into a series of 2D
horizontal cross-sections by the help of specialized slicer software, which is
installed in the 3D printer.

Now the print head is moved in the x-y axis to create the base of the 3D object.

The print head is now allowed to move in the z-axis, thereby depositing the layers
sequentially of the desired material, hence creating a complete 3D object.
Maximum numbers of 3D printing technologies are compatible with (.STL) file
format. Some errors might occur during the conversion of the 3D model to .STL
digital file; therefore, software like Magics (Materialise) can be employed to
correct the errors during conversion. File formats other than .STL like additive
manufacturing file format (AMF) and 3D manufacturing format (3MF) are used
as .STL does not have information regarding the type of material, its color, texture,
properties, and other features
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Advantages of 3D printing in the pharmaceutical field:

1. 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.

2. 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.

3. 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.

4. 3DP allows controlled size of droplets, complex drug release profiles,

strength of dosage and multi-dosing.

Disadvantages of 3D Printing:

1. In inkjet printing, proper flow of ink can only be achieved with ink that has
precise viscosity.

2. Ink formulation material should have the property of self-binding but should
not bind to other printer elements. In some formulation when the ink does
not possess adequate self-binding property or it binds with other elements of
printer then the resultant formulation does not have required hardness.

3. Rate of drug release may get affected due to binding of ink with other printer
materials
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Medical applications of 3D printing

1. Bioprinting of tissues and organs

One of the critical medical issues is the failure of organs and tissues as a result of
accident, congenital defects, aging etc and the current resolution for this problem
is organ transplant from dead or living donors. However, only few fortunate people
receive organs and the rest die due to donor shortage. Moreover, the procedures for
organ transplants are so expensive that it is out of reach of common people.
Another problem with transplant surgery is that donors with tissue match are
difficult to find. The solution to this problem lies in the fact that the required tissue
or organ should be fabricated using the patient’s own body cells, which would
decrease the risk of tissue or organ rejection; moreover, the requirement for
immunosuppressant will also be greatly reduced.
In the conventional method of tissue engineering from a small tissue sample, stem
cells are isolated, amalgamated with growth factor, and then multiplied in the
laboratory. Then the cells are seeded onto scaffolds that direct cell proliferation
and differentiation into a functioning tissue. Placement of cell with accuracy,
digitally controlled speed, drop volume, resolution, concentration of cells and
diameter of printed cell are some of the additional advantages that 3D bioprinting
offers over traditional tissue engineering.
Depending upon the porosity, the type of tissue, and required strength, various
materials are present to make the scaffolds. Among all materials, hydrogels are
said to be the most suitable for building soft tissues. No doubt that organ printing is
still in the phase of development but several researches have demonstrated its
concept with proof. Scientists have built an artificial ear, cartilage and bone, and
heart valve by the help of 3D printers. Wang et al. used 3D bioprinting technology
to deposit different cells within various biocompatible hydrogels to produce an
artificial liver. As with the increasing interest of researcher and academician and
with vast potential of this technology it can possibly unfold new potential
therapeutic drugs thereby greatly cutting research cost and time.
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2. 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.

3. Personalized drug dosing

Increasing the efficacy of drugs and at the same time reducing the chances of
adverse reaction should be the aim of drug development, which can be achieved by
using 3D printing to fabricate personalized medication.
Oral tablets are prepared by mixing, milling, and dry and wet granulation of
powder ingredients, which are eventually compressed to form tablets; till today,
tablets are the most popular dosage form because of the ease of preparation, good
patient compliance and accurate dosing and because they are painless. However,
no method is available that can prepare personalized solid dosage forms like
tablets.
In the traditional way of preparing tablets, drugs can easily undergo degradation if
proper guidelines are not followed, leading to altered therapeutic value of the final
product. Moreover, these conventional methods cannot be used to prepare
customized dosage forms that possess long-lasting stability, novel drug release
profile, and detailed geometries.
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.
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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.

4. 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 [55]. 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
In a research concerning drug release profiles, chlorpheniramine maleate was 3D
printed onto a cellulose powder substrate in amounts as small as 10–12 moles to
demonstrate that even a minute quantity of drug could be released at a specified
time. This study displayed improved accuracy for the release of very small drug
doses compared with conventionally manufactured medications

5. Customized implants and prostheses

By the support of MRI, CT scan, and X-ray and its translation into .stl 3D print
files, implants and prostheses of any possible shape can be made Standard as well
as complex surgical implants and prosthetic limbs can be made as per need in time
as less as 24 hours. Spinal dental and hip implants have been fabricated so far but
their validation is a time-consuming process. Previously, in order to achieve a
desired shape and size that fits perfectly, surgeons had to craft metal and plastic
pieces and perform bone grafting or use drill machines to modify the implants.
This also stands correct in neurosurgery cases due to the irregular shape of the
skull whose standardization is a complex procedure. Some examples of
commercially and clinically successful 3D printed implants and prostheses are as
follows:
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a. First 3D printed titanium mandibular porsthesis was implanted successfully at

BIOMED Research Institute in Belgium
b. Dental, orthopedic, maxillofacial, and spinal implants are manufactured by a
company named Layer Wise
c. Invisalign braces is another successful commercial use of 3D printing.
By using silver nanoparticles, chondrocytes, and silicon, a prosthetic ear was made
out of 3D printing technology that was able to detect electromagnetic frequencies.
The impact of this technology is so extensive in the field of hearing aids that today
99% of customized hearing aids are made using 3D printers, because, as
everyone’s ear canal has a different shape, this technology is able to provide
perfect fit for each receiver and, moreover, the devices can be produced efficiently
and cost effectively

6. Anatomical models for surgical preparations

In order to have successful medical procedures, knowledge about patients’ specific
anatomy before medical surgery is essential due to variations in individual and
complex human anatomy. 3D printed models have helped extensively in this
respect, making them a vital tool for surgical methods
One of the most complicated structures of human body is the head, whose 3D
printed neuro-anatomical models are of great help to neurosurgeons. Sometimes, it
is very difficult to gain detailed information about the connections between skull
architecture, cerebral structure, cranial nerves, and vessels from radiographic 2D
images only and even a slight error in the medical procedure can be fatal. Here
comes the role of 3D models, which are more realistic and provide in detail
comparison and contrast between a normal brain structure and a brain with
deformity or lesions, which suggest the surgeons more safe procedures to follow:
• For liver transplant, Japan’s Kobe University Hospital had used 3D printed
models by using replica of patients’ own organ, to find out how to precisely craft a
donor liver with least tissue loss.
• 3D printed model of calcified aorta for surgical planning of plaque removal was
used by surgeons.
• To study aerosol drug delivery to lungs, airways of premature infants was
reconstructed using 3D printing technology
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CONCLUSION

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.