2. Introduction.
Scope and Objectives.
Experimental approach.
Example of marketed preparation.
References.
3. 3-Dimensional (3D) printing, also known as additive
manufacturing (AM), fabricates a structure via deposition,
binding or polymerisation of materials in successive layers
until the complete object is created.
The efforts and advances of AM technology in the field of
pharmaceutics has recently culminated with the US Food
and Drug Administration (FDA) approval of the world’s
first AM orodispersible tablet SPRITAM® (Levetiracetam),
further supporting the capabilities of AM to improve upon
current pharmaceutical dosage forms through complex and
customized dosage forms which are not cost-effective or
otherwise impossible with traditional manufacturing.
4.
5.
6. The inclusion of additive manufacturing (AM) technology,
more commonly known as 3D printing, in the manufacture
of oral dosage forms such as tablets, provides an avenue for
the implementation of precision medicine in current
healthcare practice via the prescription of specific dosage
forms and drug combinations tailored to individual needs.
Thus , many of the problems associated with the “one-size-
fits-all” approach to the manufacture of pharmaceuticals
can be addressed by tailoring medications and dosage forms
to the environment, lifestyle, and genetics of each patient.
With recent advances in AM of medications, the healthcare
industry may have a solution for achieving personalization
of pharmaceutical care for patients.
7. Additive Manufacturing technologies, with their ability to
selectively deposit and/or fuse (multiple) materials in a layer-
wise manner, affords reproducible creation of personalized
pharmaceutical dosage forms by utilizing precise control of
factors such as droplet size to control the dose and API
compartmentalization to create complex drug release profiles.
As such, this technology offers the ability to decrease pill burden,
decrease the prevalence of polypharmacy, increase patient
adherence, increase provider flexibility of dosing, and ultimately
tailor individual therapeutic regimens to the unique needs of each
patient.
This is especially compelling for the management of chronic
disease states such as neurologic disorders, diabetes,
hyperlipidemia, chronic pain, psychiatric disorders, or
cardiovascular disease in which providers often face the
challenge of patient variability related to age, weight, race,
kidney and liver function.
8. There are 5 main classes of AM technologies beginning
with the vat polymerisation, following by powder bed
fusion, material extrusion, material jetting and finally
direct energy deposition.
Each has its unique working principles that may
sometimes restrict the type of material available for use
in that technology. The green ticks refer to technologies
that have been used for pharmaceutical applications
either in actual product or in research.
9.
10. Vat Photopolymerisation:- Vat polymerisation uses a
vat of liquid photopolymer resin, out of which the model is
constructed layer by layer. An ultraviolet (UV) light is used
to cure or harden the resin where required, whilst a platform
moves the object being made downwards after each new
layer is cured.
As the process uses liquid to form objects, there
is no structural support from the material during the build
phase., unlike powder based methods, where support is
given from the unbound material. In this case, support
structures will often need to be added. Resins are cured
using a process of photo polymerization or UV light, where
the light is directed across the surface of the resin with the
use of motor controlled mirrors. Where the resin comes in
contact with the light, it cures or hardens.
12. Powder Bed Fusion:- The Powder Bed Fusion
process includes the following commonly used printing
techniques:
Direct metal laser sintering (DMLS),
Electron beam melting (EBM),
Selective heat sintering (SHS),
Selective laser melting (SLM) and
Selective laser sintering (SLS).
Powder bed fusion (PBF) methods use either a laser or
electron beam to melt and fuse material powder together.
All PBF processes involve the spreading of the powder
material over previous layers. There are different
mechanisms to enable this, including a roller or a blade. A
hopper or a reservoir below of aside the bed provides fresh
material supply. The process sinters the powder, layer by
layer. Layers are added with a roller in between fusion of
layers. A platform lowers the model accordingly.
14. Material Extrusion:- Material is drawn through a
nozzle, where it is heated and is then deposited layer by
layer. The nozzle can move horizontally and a platform
moves up and down vertically after each new layer is
deposited. It is a commonly used technique used on many
inexpensive, domestic and hobby 3D printers.
The process has many factors that influence the final
model quality but has great potential and viability when
these factors are controlled successfully. Whilst FDM is
similar to all other 3D printing processes, as it builds layer
by layer, it varies in the fact that material is added through a
nozzle under constant pressure and in a continuous stream.
This pressure must be kept steady and at a constant speed to
enable accurate results. Material layers can be bonded by
temperature control or through the use of chemical agents.
17. Material Jetting:- Material jetting creates objects in a
similar method to a two dimensional ink jet printer.
Material is jetted onto a build platform using either a
continuous or Drop on Demand (DOD) approach.
Material is jetted onto the build surface or platform,
where it solidifies and the model is built layer by layer.
Material is deposited from a nozzle which moves
horizontally across the build platform. Machines vary in
complexity and in their methods of controlling the
deposition of material. The material layers are then cured or
hardened using ultraviolet (UV) light.
As material must be deposited in drops, the number of
materials available to use is limited. Polymers and waxes
are suitable and commonly used materials, due to their
viscous nature and ability to form drops.
19. Directed Energy Deposition:- Directed Energy
Deposition (DED) covers a range of terminology:
‘Laser engineered net shaping, directed light
fabrication, direct metal deposition, 3D laser cladding’
It is a more complex printing process commonly used
to repair or add additional material to existing
components.
A typical DED machine consists of a nozzle
mounted on a multi axis arm, which deposits melted
material onto the specified surface, where it solidifies.
The process is similar in principle to material extrusion,
but the nozzle can move in multiple directions and is
not fixed to a specific axis. The material is melted upon
deposition with a laser or electron beam.
25. Lim H. S. et. al.; “3D printed drug delivery and testing
systems — a passing fad or the future?”. Advanced
Drug Delivery Reviews, 2018; vol. 05; issue 006; pp.
no. 5,6,10,11,14,16,18.
Trivedi M. et. al., “Additive manufacturing of
pharmaceuticals for precision medicine applications: A
review of the promises and perils in implementation”.
2018; vol. 07; issue 004; pp no. 3,4.
https://additivemanufacturing.com/basics/
https://www.whiteclouds.com/3dpedia/vat-
polymerization/
