3D PRINTING IN PHARMACEUTICAL

RESEARCH

Presented by :
MIHIR PATEL
M.PHARMA (PHARMACEUTICS)
INTRODUCTION
 It is called as ADDITIVE MANUFACTURING PROCESS.
 An object is created by laying down successive layers of material until
the entire object is created.
 Each layers is seen as a THINLY SLICED HORIZONTAL
CROSSSECTION of the eventual object.
 FDA‘s approved a 3D-printed drug product in August 2015 in
pharmaceutical field.
 The U.S. Food and Drug Administration agency (FDA) granted the
approval of Spritam (levetiracetam)
 SPRITAM : The first 3D printed tablet for the treatment of epileptic
seizures.
HISTORY
 Charles W. Hull - The father of 3D printing, created and patented its earliest
incarnation in 1984.
 His invention, STEREO LITHOGRAPHY,‘‘Slicing a computer-aided design
(‘CAD’) file into two-dimensional crosssections and used an ultraviolet laser to
‘print’ the crosssections layer by layer in a photosensitive resin.”
 In 2004, Adrian Bowyer started the RepRap project, an ongoing online
community initiative relying on open source design to create affordable 3D
printers.
 The FIRST DIY-TYPE 3D PRINTER to use injection molded plastic parts,”
could print nearly all the parts required to self-replicate.
 MakerBot is one of the most recognized names in the commercial 3D printer
industry
Types of pharmaceutical 3D printing systems

● The five components

of a digital pharmacy
era
Develop: Printlets are developed by inserting the required ‘ink’ cartridge (composed
of a mix of drug and excipients) into the selected 3D printer. The most appropriate
printing parameters are selected (e.g. resolution, temperature, printing time), which
are typically based on the printer type, drug characteristics and desired outcomes;

Design: Using digital computer-aided design software, the pharmacist can design
the formulation — for example, selecting the printlet geometry (shape and size) that
can be targeted to the pre-clinical or clinical requirements. The designed formulation
is then digitally transferred to the selected 3D printer;

Dispense: The 3D printer is then ready to automatically prepare the printed

formulations layer by layer, which are then ready for ‘dispensing’ by the pharmacist.
APPLICABLE 3D PRINTING METHODS

● Selective laser sintering (SLS)

● Stereolithography (SLA)
● Direct powder extrusion (DPE)
● Semi-solid extrusion (SSE)
● Fused deposition modelling (FDM)
● Binder jet printing (BJ)
SELECTIVE LASER SINTERING (SLS)
This process employs a laser that is directed
to draw a specific pattern on the powder bed,
causing selective partial or full melting to
bind powder particles. Once the layer is
sintered, a roller distributes a fresh layer of
powder on top of the sintered material. The
process is repeated layer-by-layer to
fabricate a 3D-printed medicine.

SELECTIVE LASER SINTERING (SLS)

SREREOLOTHOGRAPHY (SLA)
The process involves exposing a
photopolymerisable resin to high-energy light
(e.g. UV light) to induce polymerisation and
solidification of the material. Each time, the
resin is solidified to a defined depth, the
platform is moved down vertically along the z-
axis and the built layer is recoated with resin.
The process is repeated to create a 3D-printed
medicine.

SREREOLOTHOGRAPHY (SLA)
DIRECT POWDER EXTRUSION (DPE)
An extrusion-based process, a drug loaded
formulation blend is inserted into a powder
hopper. The hopper feeds into a heated single
screw extruder in the print head, creating a
molten extrudate, which solidifies at room
temperature onto a build plate. The build plate is
sequentially lowered along the vertical z-axis to
enable a layer-by-layer fabrication of a 3D-printed
medicine.

DIRECT POWDER EXTRUSION (DPE)

SEMI-SOLID EXTRUSION (SSE)
A drug-loaded semi-solid material (e.g. gel or paste)
is extruded using a syringe-based tool head. The
printer head is moved along the x-y-z axis to release
the extrudate, which solidifies at room temperature
onto a build plate.

SEMI-SOLID EXTRUSION (SSE)

FUSED DEPOSITION MODELLING (FDM)
A drug-loaded filament is extruded through a
heated nozzle. The printer head is moved along
the x-y axis to release the molten extrudate, which
solidifies at room temperature onto a build plate.
The build plate is sequentially lowered along the
vertical z-axis to enable a layer-by-layer fabrication
of a 3D-printed medicine.

FUSED DEPOSITION MODELLING (FDM)

BINDER JET PRINTING
A nozzle containing a binder liquid moves along an
x-y axis depositing the liquid onto a flat powder
surface. The liquid binds the powder particles
together, causing layer solidification. The
fabrication build plate is then moved down along
the vertical z-axis. A thin powder layer is
distributed on top and the process is repeated
sequentially to fabricate a 3D-printed medicine.

BINDER JET PRINTING

MATERIAL REQUIREMENT IN 3D PRINTING IN PHARMACY
● In discussing 3D printed pharmaceuticals, it is also important to consider the type
of material – whether it be
● a powder, solid bulk, or liqued substance – that is used to print the drug product.
● SLS and binder deposition both require a powder substance.
● Compatible with extrusion-based printing, fused deposition modeling (FDM) relies
on the extrusion of solid laments loaded with the desired drug.
● Due to the reliance on solid polymer-based filaments, this method poses more
challenges in making it appropriate for oral dosage medicines.
● Conversely, natural and synthetic hydrogels have a more viscous consistency that
makes them more appropriate for oral drug products.
MATERIALS FOR POWDER-BASED PRINTING
● Factors that impact the printability include particle size, binder viscosity, droplet
size of the binder solution, the concentration of the binder solutions, and the
thickness of each powder layer.
● The powder size must not be too small as to cause low flowability, nor may it be too
large such that high density printed parts are not feasible.
● The binder solution must be of low enough viscosity and high surface tension to
precisely form small droplets, while also being able to penetrate the layer of powder
● The binder-powder mixture may either dry to form the solid part, or the materials
may react to cause localized polymerization, curing or bonding.
● Powders may include soluble polymers, plastics and starches, while binders
include chloroform and water, among other solvents
FUSED DEPOSITION OF SOLID MATERIALS
● Fused deposition modeling (FDM) 3D printers are a specific category of extrusionbased
printers which use a solid, polymer lament.
● The filament is fed through an electronically controlled nozzle which melts the lament
and deposits it onto the print bed where the melted filament solidifies into the final 3D
printed form.
● Such printers are simple and versatile, and are compatible with laments such as
poly(lactic acid) (PLA), poly(vinyl alcohol) (PVA), and ethylene vinyl acetate (EVA).
● Due to the polymer nature of the laments, they exhibit considerable structural stability
after printing and solidifying.
● These filaments are also largely water-soluble, and are capable of being loaded with a
drug in solution.
● Filament can be loaded with varying con-centrations of drugs for specified doses by
dissolving the drug in an ethanolic solution and submerging the unprinted, solid filament
in the solution
NATURAL AND SYNTHETIC HYDROGELS
● As opposed to the solid nature of polymer-based filaments used in FDM printing,
hydrogels are viscous and capable of being extruded or deposited as droplets via
extrusion-based printing and inkjet-based printing, respectively.
● Implementing a controllable gelling hydro-gel system, many layers of drug-
loaded hydrogels can be printed into 3D structures, characterized by pores and
channels which can be printed into the materials.
● Following printing, curing and soaking, the hydrogel patterns develop into water-
swollen networks formed by the deposited hydrogel materia
PAEDIATRICS
• The ability to produce medicines with personalised
dosage, flavour, shape and size can provide many
benefits to paediatric populations, for whom conventional
mass-produced formulations may not be suitable (e.g.
owing to poor palatability or unsuitable dosages). Several
studies have focused on producing child-acceptable
formulations using 3D printing, including the production of
chewable and even chocolate-based formulations.

• For example, a 2018 study by Scoutaris et al. produced

‘candy-like’ formulations of several drugs, including
indomethacin, that imitatedHaribo Starmix® sweets using
FDM. However, while 3D printing can create formulations Chewable printlets in different flavours, colours and with
that are palatable to children, it is important to balance different doses of isoleucine for the world-first clinical
study using 3D printed chewable tablets to treat
this against the risk of the formulations being too children with maple syrup urine disease
desirable and creating unintended risks to patient safety.
OLDER PEOPLE
• 3D printing may be beneficial to older populations or
for those on complex dosing regimens where
polypharmacy is common, leading to a high tablet
burden. Studies have highlighted that polypharmacy
can lead to non-adherence and confusion for
patients, posing a risk of dosing errors.

• 3D printing technologies may improve medicines

independence. SLS has been employed to prepare
orally disintegrating printlets with Braille and moon
patterns on the surface of the dosage forms to
enable visually impaired patients to identify
medications. The printlets were also produced in
different shapes to offer additional information, such
as the dosing regimen.
Photographs of orodispersible printlets produced
using SLS 3D printing, which have the Braille alphabet
(A) and Moon alphabets (B) imprinted on their
surface. The study also demonstrated the ability to
produce printlets of different shapes (C), including
those in the shape of a caplets, heart-shaped tablet,
sun and moon.
ADVANTAGES OF 3D FOR DRUG MANUFACTURING
• 3D printing enables increased geometric and architectural complexity, facile fabrication of multi-layer delivery
systems, and the application of various controlled release mechanisms.

• Theoretical scheme of 3D printing for drug manufacturing. Based on a patient’s speci c prescription from his
doctor, a custom medication is designed via computer-aided design. The dosage form may be composed of
complex geometries, multiple doses, or even multiple drugs. Drug-loaded bioink (biocompatible material) is
then 3D printed ondeman
● Printing as an approach for drug manufacturing also introduces precise and
unique dosing, and the ability to create multi-dose or multi-drug pharmaceutical
products.
● Dosing may also be tailored specifically for individual patients
● The printing of drugs makes point-of-care, pharmacy-based drug production
possible, without the risks and extensive fabrication time associated with com-
pounding pharmacies.
● Release Characteristics of Drugs.
● Precise and Unique Dosing
● On-Demand Capabilities
CONCLUSION
3D printing has the potential to revolutionise clinical pharmacy practice. It can
transition conventional means of medicine mass manufacture towards the
production of small batches of highly flexible and personalised dosage forms on-
demand. This technology provides benefits for patients, pharmacists and the
pharmaceutical industry alike by providing unique advantages such as making
treatments safer and more effective. Healthcare professionals, including
pharmacists, doctors, and nurses, are of paramount importance in enabling the
integration of this technology and will be key to advising academics, the
pharmaceutical industry and biotech companies on strategies to innovate the
sector using 3D printing.