Practice School Report

Study of 3D printing in pharmaceutical

In partial fulfillment of the requirements for the degree of

Bachelor of Pharmacy
By

Rupesh Kumar Yadav

(Roll. No. 1909090500030)

Dr. A.P.J. Abdul Kalam Technical University, Lucknow(UP)

Submitted To Submitted By
Mr.Mohd. Shaiber Siddique Rupesh Kumar Yadav
Assistant Professor B.Pharm IV year

Maa Bhagwati College of Pharmacy, Chinhat, Lucknow

DECEMBER 2022
 DECLARATION

I hereby declare that the work presented in this report entitled “study of 3D
printing in pharmaceutical” was carried out by me I have not submitted the
matter embodied in this report for the award of any other degree or diploma of
any other university or institute.

I have given due credit to the original author/sources for all the word, idea,
diagrams, graphics, computer programs, experiment, result, that are not my
original contribution.

I have use quotation marks to identify verbatin sentences and given credit to the
original author/sources.

I affirm that no portion of my work is plagiarized, and the experiment and result
reported in the report are not manipulated. In the event of a complaint of
plagiarism and the manipulation of the experiments and result. I shall be fully
responsible and answerable.

Rupesh kumar yadav

Roll No. 1909090500030

B.Pharm IV year

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 CERTIFICATE

Certificate that Rupesh Kumr Yadav (Enrollment no.:-190909050068990)

has carried out the research work presented in this project entitled “Study of 3D
printing” for award of Bachelor of Pharmacy, from Dr. APJ Abdul Kalam
Technical University, Lucknow under my supervision. The project embodies
result of original work, and studies are carried out by the student himself and the
contains of the project do not for the basis for the award of any other degree to
the candidate are to anybody else from this or any other university/institutions.

Signature

Mr. Mohd. Shaiber Siddique

Maa bhagwati college of pharmacy, assistant professor

Date :-

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 CERTIFICATE

This is certified that the synopsis entitled “Study of 3D printing ” submitted to

Maa Bhagwati college of pharmacy for the partial fulfillment of Bachelor
Degree in Pharmacy is to bonafied and original research work carried out by
Rupesh Kumar Yadav under my supervision and guidence for Mr. Mohd.
Shaiber Siddique Department of Pharmacy, Maa Bhagwati college of
pharmacy

Dr. Harikesh Maurya

Principal , Faculty of Pharmacy

Maa Bhagwati college of pharmacy

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 ACKNOWLEDGEMENT

I consider myself lucky to work under the guidance of Mr. Mohd. Shaiber
Siddique as their Continuous guidance and support have always propelled me to
perform better. I am thankful to her encouragement and support, which provide to
impetus and paved the way for the successful completion of this research work. It is
my privilege to express my heartfelt thanks to Mr. Mohd. Shaiber Siddique and
Principal, Maa Bhagwati College Of Pharmacy, Satrik Road Juggaur Chinhat
Lucknow or providing me all facilities and encouragement throughout the research
work.

At the outset, I would like to express my sincere to all those who have directly or
indirectly helped me in making my project a success. And above all, words fail to
express my feeling to my parents, whose initiation, constant source of inspiration
and encouragement throughout this course. The most thanks to my parents and my
family who have always been my backbone in all my endeavors, their belief in me
makes me accomplish every task I undertake. A warm to thanks to all.

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 TABLE OF CONTENTS

S. NO. TOPIC PAGE

NO.
1. Declaration I
2. Certificate II-III

3. Acknowledgement V

4. Introduction of 3D printing 1-2

5. The future of 3D printing in medicine 3-4

6. Method of 3D printing 5-12

7. Advantage and challenges 13-15

8. Application 16

9. Reference 17

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 GENERAL INTRODUCTION OF 3D PRINTINNG

Three-dimensional (3D) printing is causing a paradigm shift in pharmaceuticals and

clinical pharmacy practice, transitioning away from the traditional mass production of
medicines towards tailored drug products that are personalized to each individual. The
concept has the potential to provide benefits for patients, pharmacists and the
pharmaceutical industry alike by enabling the on-demand design and production of
flexible formulations with personalized dosages, shapes, sizes, drug release and multi-
drug combinations. This is a turning point in the history of 3D printing technology in
pharmaceuticals, requiring the engagement and support of healthcare staff, including
pharmacists, doctors, nurses and pharmacy technicians, among others, to enable the
widespread translation of the technology into clinical practice.

In recent years, the concept of personalized medicine has emerged, which involves the
tailoring of medical treatment to each individual patient. Conventionally, medicines
are mass manufactured in a limited number of discrete strengths, largely using
technologies that were invented more than 200 years ago. Crucially, the selected
dosing regimens represent the required dose for the safe and therapeutic effect in the
‘average’ patient. However, it has become evident that one dose does not fit all; in the
UK, up to 70% of patients do not gain efficacy from traditional mass manufacturing
approaches, with 90% of drugs only working in 30–50% of the population and 7% of
hospital admissions resulting from adverse drug reactions.

In 2015, the US Precisions Medicine Initiative was launched to understand how a

patient’s genetics, environment, and lifestyle can help determine the best approach to
prevent or treat disease. Personalized medicine has also been placed at the forefront of
the UK healthcare agenda. These initiatives are outlining how to move away from the
‘one-size-fits-all’ approach towards personalization, requiring medication to be
tailored to individuals, considering factors such as physiology, concurrent therapy,
drug response, genetic makeup, disease state and other factors (e.g. sex, weight and
age). Personalizing treatments by tailoring medicines (e.g. combining more than one

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drug into the same tablet or selecting appropriate dosages) offers a plethora of
opportunities including improved medication adherence, reduced adverse drug
reaction and better therapeutic outcomes.

Fig-1

THE FUTURE OF 3D PRINTING IN MEDICINE

Three-dimensional (3D) printing has provided individuals in various industries with a

tool to bring their creations to life. The medical field is no stranger to 3D printing,

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which has been utilized in various applications since its inception. The various
additive technologies currently available to elucidate the differences between them
will be discussed briefly. The current applications of 3D printing in medicine could be
divided into applications in medical education, patient care, equipment modification
or fabrication, and research. The various applications in these categories are described
with examples of upcoming research and technology that may be available in the near
future. Despite the benefits of 3D printing, challenges remain, and technology
improvements are required before there will be more adoption in the medical field.
The technology is growing rapidly and evolving, and more 3D printing applications
will be seen in the future.

There has always been a desire to manifest ideas into physical objects, and three-
dimensional (3D) printing has brought us closer than ever to that goal. Although 3D
printing was conceptualized in the 1970s and has been available since the 1980s, it has
not truly had as large an impact as it had in the last few years. This has been due to the
price decrease in 3D printers and printers that are now produced commercially, which
enables them to be used by an increasing number of people.

Early adopters of this technology were enthusiasts and finding people with
technological experience in setting up and running 3D printers was challenging. As
the printers became more user friendly, the amount of software developed to improve
user experience adoption increased. 3D printing was found in health care, from
researchers to front liner staff during COVID-related printing, which included items,
such as protective equipment and other applications in various specialities that are
found in the literature.

Although it has proven to be a valuable tool, the current technology has limitations in
applications with printing time and materials that impact its practicality. In this article,
an insight into the various 3D printing technologies currently available will be
provided and some of the applications in various specialities of medicine will be
discussed and how they impact current practice and future directions. The use of 3D
printing in medical applications has great promise for the future; however, significant

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barriers exist to successful implementation, regardless of scientific knowledge. The
goal of research is to successfully 3D print organs for transplant, and soon there might
be breakthroughs that allow autologous 3D printed organs that use a patient’s cells.
However, 3D printing the complex cytoarchitecture of organs remains difficult.
Furthermore, 3D printing could be used more as a teaching tool. For pharmacology,
research into 3D printed patient-specific medicine is expected to expand, and
companies, such as Curifylabs have developed an automated digital technology
(Curify MiniLab) to 3D print medicines; however, the potential of multiple
formulations in one tablet is unknown. For medical companies, research into
modifying existing products to facilitate 3D printing, and expanding the range of
materials that can be 3D printed, would be a logical direction for research, in addition
to improvements in the efficiency and speed of 3D printing.3D printing drugs is not a
fantasy anymore. Unbelievable shapes and any kind of drug can be fabricated with
groundbreaking technology. The UK biotech company, FabRx believes it could even
appear as a regular technique in hospitals and pharmacies for creating personalized
drugs in specific doses within 5-10 years. In February 2022 the company announced
they developed a technology allowing them to 3D print tablets in 7-17 seconds, a huge
improvement from earlier.

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 Fig-2

METHOD OF 3D PRINTING

The challenge that many newcomers to 3D printing face is distinguishing between the
different processes and materials available. What’s the difference between types of 3D
printing like FDM and SLS, for example? Or SLS and binder jetting? Or EBM and
DMLS? It can be pretty confusing, and with so many different acronyms flying
around, you’d be forgiven for mistaking a type of 3D printing for a genre of dance
music.

Truth is, 3D printing, also commonly referred to as additive manufacturing, is an

umbrella term that encompasses a group of different 3D printing processes. In 2015,
the ISO/ASTM 52900 standard was created with the aim to standardize all
terminology and classify each of the different types of 3D printers.

1. Fused Deposition Modeling (FDM)

Material Extrusion devices are the most commonly available – and affordable – types
of 3D printing technology globally. The way it usually works is that a spool of
filament is loaded into the 3D printer and fed through to a printer nozzle in the
extrusion head. The printer nozzle is heated to the desired temperature, whereupon a
motor pushes the filament through the heated nozzle, causing it to melt. The printer
then moves the extrusion head along with specified coordinates, laying down the
molten material onto the build plate, where it cools down and solidifies. Once a layer
is complete, the printer proceeds to lay down another layer. This process of printing
cross-sections is repeated, building layer-upon-layer until the object is fully formed.

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Depending on the object’s geometry, it is sometimes necessary to add support
structures, for example, if a model has steep overhanging parts.

fig-3

2. VAT POLYMERIZATION

Vat polymerization is a 3D printing process where a light source selectively cures a

photopolymer resin in a vat. In other words, light is precisely directed to a specific
point on a thin layer of liquid plastic to harden it. This process is repeated layer by
layer until the 3D part is formed. Three common forms of vat polymerization are
stereo lithography (SLA), digital light processing (DLP), and masked stereo
lithography (MSLA). The fundamental difference between these types of 3D printing
technology is the light source they use to cure the resin and we detail each method
below.

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 Types of 3D Printing Technology: Stereo lithography (SLA), masked stereo
lithography (MSLA), microstereolithography (µSLA), and more.

 Materials: Photopolymer resins (cast able, transparent, industrial, biocompatible,

etc.)

 Dimensional Accuracy: ±0.5% (lower limit ±0.15 mm or 5 nanometers with µSLA)

 Common Applications: Injection mold-like polymer prototypes; jewelry casting;

dental applications

 Strengths: Smooth surface finish, fine feature details

fig-4

3. Stereo lithography (SLA)

SLA holds the historical distinction of being the world’s first 3D printing technology.
Stereo lithography was invented by Chuck Hull in 1986, who filed a patent on the
technology and founded the company 3D Systems to commercialize it. An SLA
printer uses mirrors, known as galvanometers or galvos, with one positioned on the X-
axis and another on the Y-axis. These galvos rapidly aim a laser beam across a vat of
resin, selectively curing and solidifying a cross-section of the object inside this
building area, building it up layer by layer. Most SLA printers use a solid-state laser to
cure parts. The disadvantage of these types of 3D printing technology using a point

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laser is that it can take longer to trace the cross-section of an object when compared to
our next method (DLP), which hardens an entire layer at once.

fig-5

4. Digital Light Processing (DLP)

Looking at digital light processing machines, these types of 3D printers are almost the
same as SLA. The key difference is that DLP uses a digital light projector to flash a
single image of each layer all at once (or multiple flashes for larger parts). Because the
projector is a digital screen, the image of each layer is composed of square pixels,
resulting in a layer formed from small rectangular blocks called voxels. Light is
projected onto the resin using light-emitting diode (LED) screens or a UV light source
(lamp) that is directed to the build surface by a digital micro mirror device (DMD). A
DMD is an array of micro-mirrors that control where light is projected and generate
the light-pattern on the build surface.

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 Fig-6

5. Direct Metal Laser Sintering (DMLS) / Selective Laser

Melting (SLM)

Both direct metal laser sintering (DMLS) and selective laser melting (SLM) produce
objects in a similar fashion to SLS. The main difference is that these types of 3D
printing technology are applied to the production of metal parts. DMLS does not melt
the powder but instead heats it to a point so that it can fuse on a molecular level. SLM
uses the laser to achieve a full melt of the metal powder forming a homogeneous part.
This results in a part that has a single melting temperature (something not produced
with an alloy). This is the main difference between DMLS and SLM; the former
produces parts from metal alloys, while the latter forms single element materials, such
as titanium. Unlike SLS, the DMLS and SLM processes require structural support to
limit the possibility of any distortion that may occur (despite the fact that the
surrounding powder provides physical support).

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 Fig-7

6. Electron Beam Melting (EBM)

Distinct from other powder bed fusion techniques, electron beam melting (EBM) uses
a high energy beam, or electrons, to induce fusion between the particles of metal
powder. A focused electron beam scans across a thin layer of powder, causing
localized melting and solidification over a specific cross-sectional area. These areas
are built up to create a solid object. However, things like minimum feature size,
powder particle size, layer thickness, and surface finish are typically larger. Also
important to note is that EBM parts are fabricated in a vacuum, and the process can
only be used with conductive materials

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 Fig-8

7. Multi Jet Fusion (MJF)

Multi Jet Fusion is technically a powder bed fusion 3D printing technology although it
has similarities to binder jetting. MJF was introduced to the market by HP in 2016.
The company explains its technology is built on decades of HP’s investment in inkjet
printing, jet table materials, precision low-cost mechanics, material science, and
imaging. The technology gets its name from the multiple inkjet heads that carry out
the printing process. The processes of material recoating and agent distribution and
heating are carried out by separate head arrays that move across the print bed in
different directions, thus allowing the user to optimize both processes independently.

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 Fig-9

Advantages and challenges of 3d printing

The utilization of 3DP as manufacturing process might provide some potential

benefits for the pharmaceutical industry as well as for patients. In regard to
customization and tailoring of pharmaceutical dosage forms, 3DP appears to have a
high potential as on-demand manufacturing process. Compared to conventional
manufacturing processes, 3DP technology seems to be rapidly adapting and flexible.
Besides the possibility of printing customized and complex structures, 3DP might
further be used to adjust the drug release characteristics of a dosage form as needed.

The implementation of 3DP might shorten the overall manufacturing chain

significantly since manufacturing steps like granulation, milling, sieving, tableting,
and coating would become redundant. Further, 3DP provides the opportunity to be set
up as an on-demand manufacturing process in community and hospital pharmacies.
The on-demand manufacturing might shorten lead times as well as decrease the

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amount of wasted material, since only small batches with the required amount of
dosage forms would be printed.

Alongside with the advantages and opportunities provided, 3DP has to overcome
major challenges. These challenges can be classified into three categories:

1. Technical challenges;

2. Regulatory challenges;

3. Good manufacturing practice (GMP) challenges.

1. Technical challenges:

Depending on the applied printing technology, printed objects might have insufficient
mechanical properties and possess a high friability, which makes the further
processing of these dosage forms rather difficult. Especially during packaging of
printed tablets defects might occur, which might lead to rejection of complete batches.
For some of the 3DP technologies like BJ or SLA, a lot of unprinted material
accumulates after the printing process. On the one hand, technical solution must be
found to avoid excessive amount of unprinted material and on the other hand
clarification is needed whether unprocessed material might be reused for further
printing. Compared to established pharmaceutical manufacturing processes, 3DP is
lacking in process control strategies. During conventional production of tablets, in-
process control (IPC) is carried out to monitor the production intensively. For 3DP
processes, IPC technologies are currently not commonly implemented, by which
printed tablets are assessed analytical after being printed. Further, 3DP is a time-
consuming process, whereas conventional tableting equipment is able to manufacture
several hundred thousand tablets per hour (depending on the scale of tablet press).

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2. Regulatory:

From a regulatory perspective, 3D-printed dosage forms have to meet the same
requirements as conventionally manufactured dosage forms. However, at this point a
big gap is existing in the regulatory framework. While for established processes
guidelines are well implemented and standardized, the process of 3DP is lacking any
guidelines from regulatory authorities. Health authorities around the world recognized
the lack of guidance and initiated the process of developing standards and defining
practical guidelines. The FDA designated two internal laboratories, the Laboratory for
Solid Mechanics as well as the Functional Performance and Device Use Laboratory
within the FDA´s Office of Science and Engineering Laboratories (OSEL), to explore
the future potential of 3DP in pharmaceutics . The work of these two units should help
to gain knowledge in the first step and to help developing standards as well as
identifying critical aspects affecting the product safety. Nevertheless, health
authorities must put more effort into defining standard processes and providing
guidance for pharmaceutical manufacturers.

Furthermore, liability as well as responsibility must be discussed in case of occurred

incidents. If it is intended to use 3DP as on-demand manufacturing process in
community and hospital pharmacies, different scenarios for supply chain are possible.
Regarding FFF technology, drug-loaded filaments must be provided by external
chemical or pharmaceutical companies and the printing process executed in the
pharmacy itself. The scenario raises the question of how incoming goods should be
tested with the equipment at the pharmacy and who would be responsible for the
release of the starting material for manufacturing .

3. GMP challenges:

Moreover, qualification standards for 3D-printer manufacturers must be defined to

meet GMP requirements. Especially, the topic of cleaning validation should be
addressed to avoid cross contamination. As long as cleaning concepts are not in place
and validated, pharmaceutical manufacturers are obliged to use 3D-printers as
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dedicated equipment. The mentioned regulatory and GMP challenges must be tackled
together by health authorities and pharmaceutical manufacturers to establish 3DP as
manufacturing process for pharmaceutical dosage forms.

Application

1. Bioprinting tissues and organoids

One of the many types of 3D printing that is used in the medical device field is
bioprinting. Rather than printing using plastic or metal, bioprinters use a computer-
guided pipette to layer living cells, referred to as bio-ink, on top of one another to
create artificial living tissue in a laboratory. These tissue constructs or organoids can
be used for medical research as they mimic organs on a miniature scale. They are also
being trialled as cheaper alternatives to human organ transplants.

2. Surgery preparation assisted by the use of 3D printed

models

Another application of 3D printing in the medical field is creating patient-specific

organ replicas that surgeons can be use to practice on before performing complicated
operations. This technique has been proven to speed up procedures and minimize
trauma for patients. This type of procedure has been performed successfully in
surgeries ranging from a full-face transplant to spinal procedures and is beginning to
become routine practice.

3. 3D printing of surgical instruments

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Sterile surgical instruments, such as forceps, hemostats, scalpel handles and clamps,
can be produced using 3D printers. Not only does 3D printing produce sterile tools,
some are based on the ancient Japanese practice of origami, meaning they are precise
and can be made very small. These instruments can be used to operate on tiny areas
without causing unnecessary extra damage to the patient. One of the main benefits of
using 3D printing rather than traditional manufacturing methods to produce surgical
instruments is the production costs are significantly lower.

Reference
1) Shahrubudin, Nurhalida, Te Chuan Lee, and Rhaizan Ramlan. "An overview on
3D printing technology: Technological, materials, and applications."
2) Pîrjan, Alexandru, and Dana-Mihaela Petroşanu. "The impact of 3D printing
technology on the society and economy." Journal of Information Systems and
Operations Management .
3) AMBROSI, Adriano; PUMERA, Martin. 3D-printing technologies for
electrochemical applications. Chemical Society Reviews, 2016, 45.10: 2740-
2755.
4) Bozkurt, Yahya, and Elif Karayel. "3D printing technology; methods, biomedical
applications, future opportunities and trends." Journal of Materials Research and
Technology 14 (2021): 1430-1450.
5) Yan, Qian, et al. "A review of 3D printing technology for medical applications."
Engineering 4.5 (2018): 729-742.
6) Vanderploeg, A., Lee, S. E., & Mamp, M. (2017). The application of 3D printing
technology in the fashion industry. International Journal of Fashion Design,
Technology and Education, 10(2), 170-179.
7) Karakurt, I., & Lin, L. (2020). 3D printing technologies: techniques, materials,
and post-processing. Current Opinion in Chemical Engineering, 28, 134-143.
8) SU, Amanda; AL'AREF, Subhi J. History of 3D printing. In: 3D Printing
applications in cardiovascular medicine. Academic Press, 2018. p. 1-10.
9) Oropallo, William, and Les A. Piegl. "Ten challenges in 3D printing."
Engineering with Computers 32.1 (2016): 135-148
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10) Whyte, D. J., Rajkhowa, R., Allardyce, B., & Kouzani, A. Z. (2019). A review on
the challenges of 3D printing of organic powders. Bioprinting, 16, e00057.

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