1. By Aman Chaudhary & Sunny Kumar Sarraf
SAP :-1000016858 & 1000016855
Subject Co-ordinator:-Dr. Jagannath Sahoo
Date:- 17th Sep.21
• Potential of 3d printing in personalized medicine
• Advantages of 3d printed drug delivery
• Disadvantages of 3d printed drug delivery
• Techniques in 3d printing
• Challenges in 3d printing technology
• Applications of 3d printing
• Conclusion and perspectives
As the population ages and rates of chronic disease rise, an increasing number of
people are taking multiple pills for several conditions, often at different times
throughout the day.
Taking the right pill at the right time can be a hassle and potentially dangerous if a
mistake is made. It is especially tough for people with dementia, for obvious
It would be convenient and safe if people could take just one pill a day – a pill that
delivers all the right medication at the right time in the right dose.
4. Three-dimensional printing is matchless method which uses computer aided drafting
technology and programming to make three dimensional objects by layering
material onto a substrate. It is a process of making three dimensional solid objects
from a digital file.
Now a days, 3D printing could be extended throughout the drug development
process, ranging from preclinical development and clinical trials to frontline medical
Different types of drug delivery systems for instance oral controlled release systems,
micro pills, microchip, drug implants, fast dissolving tablets and multiphase release
dosage forms have been developed using three-dimensional (3D) printing
5. When compared to the manufacturing methods of conventional
pharmaceutical product, it has a lot of advantages like high production rates
owing to its fast operating systems, capability to achieve high drug loading
with much desired precision and accuracy exclusively for potent drugs that
are applied in small doses; reduction of material wastage can save the cost
of production and pliability to more classes of pharmaceutical active
ingredients comprising poorly solubility in aqueous, proteins and narrow
therapeutic index drugs
The earliest research in 3D printing dates back to the late 1970s, which saw various
patents regarding the techniques of computer-aided additive manufacture,
employing different platforms.
In the mid-1980s, Charles (Chuck) Hull, also regarded as the pioneer of this
technology, invented and patented stereolithography (SLA), which is one of the
major technologies in 3D printing.
This process involved resins which were polymerized using UV light to obtain the
desired object. These SLA printers were then commercialized by 3D Systems, which
was founded by Hull.
7. Aprecia Pharmaceuticals’ Spritam (levetiracetam), an anti-epileptic drug, is the first
and only 3D-printed pharmaceutical.
It received the Food and Drug Administration (FDA) approval in 2015 and is made
using Aprecia’s proprietary ZipDose technology.
ZipDose technology uses a drop-on-solid printing technique where droplets of a
liquid binding agent are deposited by a print nozzle onto a free pharmaceutical
powder bed, unifying the free-form powder where it lands.
The bed is then lowered to allow for another layer of free-form powder to be added.
Further droplets are introduced, adding height to the nascent pill, while the
surrounding, unbound powder particles act as a support structure to prevent the
collapse of the highly porous pill structure.
8. April 2020, UK-based FabRx launched the first commercially available 3D printer
for personalized drug manufacturing.
M3DIMAKER is an extrusion-based printer that allows the print nozzle to be
changed to accommodate different dosage requirements.
Alongside the established extrusion-based fusion deposition modelling printing,
whereby the printer melts the pharmaceutical mixture and excipients through a
nozzle onto the build plate, the M3DIMAKER also uses a different extrusion-based
method developed by FabRx: direct powder extrusion (DPE).
Similar to Aprecia’s ZipDose technology, DPE deposits a powdered pharmaceutical
agent onto a print bed through a nozzle aided by a single extruder.
Both methods enable the manufacture of multiple-drug combination pills and
sustained or delayed-release tablets.
9. To date, large biopharmaceutical companies have shown minimal activity in this area.
In February 2020, Merck KGaA announced a collaboration with AMCM for the
development and production of 3D printed pharmaceuticals for clinical trials and, later,
for clinical manufacturing.
The stated goal of the partnership is to develop drugs using powder bed fusion, whereby
a laser melts and fuses powder together layer by layer. Merck and AMCM expect this to
make the manufacturing of tablets both faster and cheaper due to the avoidance of
GlaxoSmithKline has also shown interest in 3D printing of drugs, partnering with the
University of Nottingham on a study that used nozzle printing and ultraviolet curing to
produce 3D printed ropinirole tablets to treat Parkinson’s disease.
10. Potential of 3d printing in personalized medicine
One of the major potentials of 3D printing in the pharmaceutical sector is
its ability to tailor the dosage forms to individuals.
This can be done by fabricating adequate dosage forms, adjusting the
doses, combining them or by varying the release profiles of the dosage
forms according to the need of patients.
11. Dose Personalization
3D printing can offer potential in achieving flexibility of doses
according to the patient needs.
One major population group that calls for dose flexibility is the pediatric
group in which the therapeutic dose varies according to the age and
body weight of children.
Various dosage forms can be adequately modified using 3D printers to
dispense the best dose for patients.
12. In ODF formulations, this can be easily done by modulating the amount of
liquid API dispensed on the film.
ODFs can also be subjected to changes in shape and dimension to
individualize treatments .
Likewise, dose strength can be modified in other dosage forms like tablets
or patches to tailor them for patient needs.
For example, Pietrzak et al. used FDM and HME to print theophylline
tablets of doses varying from 60 to 300 mg by manipulating the printing
13. Modifying Release Profiles
3D printing can be employed to obtain dosage forms of various release profiles
which can be tailored to individual requirements.
One of the techniques to attain this is by altering tablet shapes and geometries.
Immediate release tablets of a low dose drugs were fabricated, where it was
concluded that by decreasing the tablet thickness or by generating spaces in them,
the drug release rates increased and complete release was achieved at times as low
as 5 min .
Khaled et al. developed paracetamol tablets of various geometries, namely ring and
mesh, and compared them with each other and solid tablets. Immediate release was
achieved with the mesh tablets, whereas ring and solid tablets demonstrated
14. Combination Tablets–Polypills
One of the significant applications of 3D printing in personalized
medicine is a concept of “polypill”.
A polypill composes of a combination of many drugs in a single tablet
which can be tailored for an individual undergoing polypharmacy.
Also, the drug release can be tailored as per individual needs. This
concept can widely benefit the geriatric populations, where it can
improve patient compliance and medication adherence as it reduces the
number of pills consumed in a day.
15. Khaled et al. successfully fabricated 3D printed polypills with three drugs
which could be a possible medication for diabetics with hypertension.
These pills compose of an osmotic compartment of captopril and sustained
release compartments of nifedipine and glipizide.
The same team also devised a polypill with five compartments which
represented a cardiovascular treatment regimen.
The tablet composed of aspirin and hydrochlorothiazide in two immediate
release compartments and pravastatin, atenolol, and ramipril in three sustained
High drug loading capability compared to conventional dosage forms.
Accurate and Precise dosing of potent drugs which are administered at small doses
Reduced production cost due to less wastage of materials.
Suitable drug delivery for difficult to formulate active ingredients like poor water
solubility and narrow therapeutic windows drugs.
Medication can be tailored to a patient in particular based on age, gender, genetic
variations, ethnic differences and environment.
Treatment can be customized to improve patient adherence in case of multi-drug
therapy with multiple dosing regimen.
Manufacture of small batch is feasible and the process can be completed in a single
3D printers capture minimal space and are affordable.
Problems related to nozzle are a major challenge as stopping of the
print head which affects the final products structure.
Powder printing clogging is another hurdle.
Possibility of modifying the final structure on to mechanical stress,
storage condition adaptions and ink formulations effects.
Printer related parameters and these effects on printing quality and
18. TECHNIQUES IN 3D PRINTING
There are numerous varieties of manufacturing practices intricate in 3D printing,
which are grounded on digitally organized depositing of materials (layer-by-
layer) to create free form geometries.
Thermal Ink-Jet Printing
In thermal inkjet printing, the aqueous ink fluid is transformed to vapours state
through heat, expands to push the ink drop out of a nozzle.
It is used in the preparation of drug-loaded biodegradable microspheres, drug-
loaded liposomes, patterning microelectrode arrays coating, loading drug eluting
It is also an effectual and applied method of generating films of biologics without
negotiating protein activity.
19. • Inkjet Printing
Inkjet printing known as ‘mask-less’ or ‘tool-less’ approach for its
desired structure formation mainly depends upon the inkjet nozzle
movement or substrate movement for an accurate and reproducible
In this methodology, the Ink is deposited onto a substrate either in the form
of Continuous Inkjet printing / Drop on demand printing. Hence it provides
a capability of high-resolution printing.
It has a low cost, rate of processing in printing and generation of low level
of wastes. It gives CAD information in a ‘direct write’ manner and process
material over large areas with minimal contamination.
20. Fused deposition modeling (FDM)
Fused deposition modelling (FDM) is commonly used method in 3D
printing, the materials are softer or melt by heat to create objects during
Fused deposition modeling 3D printing helps in manufacturing delayed
release print lets without an outer enteric coating and also provides
personalized medicines doses.
This 3D Printing indicates some limitations for system like lack of suitable
polymers, slow and often incomplete drug release, because of the drug
remain trapped in the polymers, miscibility of drug and additives with the
polymers used was not valued.
21. Extrusion 3D Printing
In this method the material is extruded from the automated nozzle onto
the substrate without any higher support material.
It is only utilized to fabricate tablet containing Guaifenesin act as
The components that can be extruded are molten polymers, suspensions,
Zip dose is the world’s initial and only FDA-approved, commercial-scale
3DP in current therapeutic areas for pharmaceutical manufacturing areas.
It has a distinctive digitally coded layering and zero compression practices,
used for tablet formulation with large dosage and prompt disintegration.
Hence, it helps in overwhelming a difficulty in swallowing.
22. • Hot melt extrusion (HME)
Hot melt extrusion (HME) is the method of melting polymer and drug at
elevated temperature and the pressure is employed in the instrument
sequentially for blending.
It is a continuous manufacturing technique that involves feeding, heating,
mixing and shaping.
In recent years, it has proved that Hot melt extrusion capable to optimize
the solubility and bioavailability of moderately soluble drugs.
23. CHALLENGES IN 3D PRINTING
Although proved promising results are there in drug delivery, still under the
Several challenges such as versatile use, appropriate excipient selections, post
treatment method to advance the enhancement of 3D printed products and to
magnify the application scope in novel drug delivery systems.
The built-in flexibility might be a most important resource of liability from safety
point of view for re-designing through 3 Dimensional printing.
The primary parameters are to be modified to improve quality of 3DP such as
printing rate, passes, print heads line velocity, printing layers interval time, nozzles
and powder layer distance etc.
24. APPLICATIONS OF 3D PRINTING
Potential use in improving process, modifying performance for industrial
design, aerospace, medical engineering, tissue engineering, architecture,
It mostly targets on the two potential sites to rise pharmaceutical product
development to unexplored areas, manufacturing sophisticated structures
for the delivery and personalized medicine.
In Healthcare industry to create dental implants.
On fabricating an organized release multi-drug implant for bone
Helps in Organ printing, biomaterials and cell-laden materials.
25. Conclusion and perspectives
Although the traditional pharmaceutical industry can meet most of the needs of
medicine, it still has some limitations: it cannot produce personalized/customized
tablets or create different/targeted release tablets.
3D printing allows for the creation of specific geometric shapes to realize the high
degree of customization of the pill (and its dose).
3D printing overcomes the limitations of conventional formulation techniques in
tailoring the tablet's microstructure and changing composition in different regions,
making it possible to print tablets with different release responses.
26. Combined with 3D printing technology, the drug delivery device can improve the
effect of drugs.
At present, cutting-edge papers on 3D printing are published every day, illustrating
the infinite possibilities of 3D printing.
The commercial viability of 3D printing has been proved by Spritam manufactured by
Aprecia pharma, inc.
Although 3D printing technology still has shortcomings in technologies and
materials, we believe that these problems will be solved by the progress of
We envisage that in the future, the effect of patients' medication and drug testing will
be greatly improved.
We believe that more and more pharmacies and hospitals will have 3D printing
facilities to enable on-demand printing.