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3D Printing for Drug Delivery and its Pharmaceutical Applications – Recent

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REVIEW ARTICLE

3D Printing for Drug Delivery and its Pharmaceutical

Applications – Recent Findings and Challenges
Neelima Mandloi*| Kuldeep Vinchurkar1 | Dinesh K Mishra2 | Pankaj Dixit3

Indore Institute of Pharmacy, Indore.

*Correspondence author: Neelima Mandloi,
Indore Institute of Pharmacy,
Phone: 9589031212,
E-mail: Neelimandloi@gmail.com.
How to cite this article: Mandloi N, Vinchurkar K,
Mishra DK, Dixit P. 3D Printing for Drug Delivery and
its Pharmaceutical Applications – Recent Findings and
Challenges. International Journal of Pharmaceutical
Sciences and Nanotechnology. 2022, 15(2):
MS ID: 2260
https://doi.org/10.37285/ijpsn.2022.15.2.11
ABSTRACT
3D Printing technology also known as Additive Manufacturing is a rapid prototyping
process that construct solid product with various geometrics by successive layers of
material by the use of Computer-Aided Design (CAD). The introduction of 3DP
technology in the pharmaceutical industry has opened new horizons in the research
and development of printed materials and devices. The main benefit of 3DP lies in
the production of small batches of medicines each with tailored dosages, shape,
size, and release characteristics. This paper presents the current status of research
and development in 3DP technology, background and basic procedure involved in
3DP, main components and types of 3DP, different methods and polymers used,
advantages, limitations, and applications of 3D printing technology.
Keywords
Drug delivery, 3D Printing technology, Pharmaceutical additive manufacturing,
Personalized medicine, Computer-aided design, Polymers, Fused deposition
modeling, Stereolithography, Selective laser sintering, Thermal inkjet.

Introduction
Drug delivery is a type of technique used for efficient
transport of a pharmacologically active component in the
body as desired to achieve required therapeutic efficacy
and safety. Within the last decade, considerable
attention was focused on the development of novel drug
delivery systems and patient-centric drug products. 3D
printing is considered to be the most revolutionary
customized medicine and dosing receives increasing
attention due to the high chances of undesirable side
effects.
Three-dimensional printing is a form of additive
manufacturing technology in which a 3D object is created
by laying down successive layers of material by using
Computer-Aided Design (CAD) software. Therefore, it is
also known by other terminologies such as layered
manufacturing, additive manufacturing, computer
automated manufacturing, rapid prototyping, or solid

ABBREVIATIONS: 3DP - Three-dimensional printing; ABS - Acrylonitrile butadiene styrene; AM - Additive manufacturing; API
Active pharmaceutical ingredient; CAD - Computer-aided design; EC – Ethylcellulose; FDA - Food and drug administration; FDM Fused
deposition modeling; HME - Hot melt extrusion; HPMC - Hydroxypropyl methylcellulose; PCL – Polycaprolactone;
PEG - Polyethylene glycol; PLA - Polylactic acid; PVA - Polyvinyl alcohol; PLGA - Poly(lactic-co-glycolic acid); PU – Polyurethane; PMMA
- Poly(methyl methacrylate); SLA – Stereolithography; SLS - Selective laser sintering; TIJ - Thermal inkjet; UV - Ultraviolet

592323
5924 | Int J Pharm Sci Nanotech Vol 15; Issue 2, March−April 2022

freeform technology. 3D printing uses computerized
drafting technology and programming to produce a 3D
object. The material is first ejected from a printer head
onto an x-y plane for creating the foundation of the
object. Then the printer moves along the z-axis, and a
liquid binder is ejected onto the base of the object to a
certain thickness. This process is repeated following the
computer-aided drafting instructions until the object is
built layer by layer. After treatment, the unbound
substrate is removed and the object is obtained (Maulvi,
2019; Ursan, Chiu, and Pierce, 2013; Parulski et al.,
2021).
The introduction of 3D printing technology in the
pharmaceutical industry has opened new horizons in the
research and development of printed materials and
devices. (Beg et al., 2020) Its main benefit lies in the
production of small batches of medicines each with
tailored dosages, shapes, sizes, and release
characteristics.
In contrast to the conventional method 3D printing is
more automated rapid and easy to use, customized,
sophisticated, and cost-effective (Solanki et al., 2018;
Singh et al., 2021). Indeed, the punches and dies-based
conventional tableting machines are fabricated for a
mass-production market and therefore lack in flexibility.
3D printing on the other hand provoked much interest in
pharmaceutics due to its large flexibility making it a
promising tool to produce customized drug delivery
devices including solid oral dosage forms. Moreover, the
most diversified and sophisticated drug delivery devices
for oral, dermal, and implantable administration can be
produced with high accuracy using 3D printers.
It is an effective strategy to overcome some of the
challenges of conventional pharmaceutical unit
operations (O Oyewumi, 2015). 3D printing technology
has enabled unprecedented flexibility in the design and
manufacturing of complex objects, which can be utilized
in personalized and programmable medicine (Jose and
GV, 2018).
In 3D printing, solid oral dosage forms can be printed
in a wide range of dosages release profiles, geometrics,
and size by simply modifying a digital model which
provides patients with tailored therapies. 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. It 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 poly-pill
concept. This brings about the possibility of all the drugs
required for the therapy into a single dosage form unit
(Jose and GV, 2018; Gaurav et al., 2021).
Various techniques of additive manufacturing are
such as powder bed-inkjet 3D printing, pressure-assisted
micro syringe 3D printing, fused deposition modeling,
selective laser sintering, stereolithography, etc (Jacob
et al., 2020).
Conventional Manufacturing - Conventional
manufacturing includes several steps as shown in
figure 1.
Additive Manufacturing - Additive Manufacturing
comprises the steps as shown in figure 2.

API-Exipient Preformulati Development Characterizat

Dispense
selection on optimization ion

Fig. 1. Conventional Manufacturing.

API- Patient
3D-
Exipient requireme Dispense
Printing
selection nt

Fig. 2. Additive Manufacturing.

Mandloi et al: 3D Printing for Drug Delivery and its Pharmaceutical Applications – Recent Findings and Challenges | 5925

medication, designed to disintegrate in the mouth with

Background just a sip of liquid (Vaz and Kumar, 2021).

The 3D printing technology was first introduced in the

late 1980s, during that time it was called Rapid
Prototyping technology. This is because the process was
originally conceived as a fast and more cost-effective
method for product development within the industry.
The origin of 3D printing can be traced back to 1986
when the first patent was issued for stereolithography
apparatus (SLA) belonged to Chuck Hull. He is also
considered the father of 3D printing technology (Jamróz
et al., 2018; Parulski et al., 2021).
The first 3D printing technique used in
pharmaceutics was achieved by inkjet printing (Konta,
García-Piña, and Serrano, 2017; Chandekar et al., 2019).
This first happened in the early 90s at the Massachuset
Institute Technology invented and patented by Sachs et
al (Vinchurkar, 2018).
In 2015, Food and Drug Administration (FDA)
approved the first 3D printed drug Spritam
(levetiracetam) tablet for oral use. Aprecia
pharmaceutical produced the first 3D printed dosage
form (tablet) using the Zipdose technology. Spritam is
the orodispersible formulation of the high-dose
Inventions of 3D Printing
Several inventions of 3D printing are shown in figure 3.
Basic Procedure Involved in 3D Printing
3D printing has several types such as Fused Deposition
Modeling (FDM), Thermal Inkjet (TIJ) Printing,
Stereolithography, Selective Laser Sintering (SLS).
In 3D printing first, the product is designed using
Computer-Aided Design (CAD) or animation modeling
software. Then the design is converted into a 3D printer
readable format which depicts the outer surface of the 3D
printed dosage form.
The computer program then slices this surface into
several printable layers which are transferred layer by
layer to the 3D printer. As illustrated in Fig 4. Some
products may require post-processing steps such as
polishing and drying. Unused materials can be recycled
to reuse for another printing cycle (Haris et. al.,2020).

First FDA
Inkjet photo-
First 3DP approved
polymerization
prosthetic 3DP drug
based printing
leg product
SLS Powder Bed printing First 3DP (Spritam)
SLA exoskeleton

1984 1986 1988 1992 1996 2000 2002 2008 2012 2014 2015 2018

First Introduction
functional First
FDM First Inkjet Printer prosthetic of 4D
miniature printing
3D printed jaw
kidney

Fig. 3. Inventions of 3D Printing.

Pharmaceutical product is Computer programs such as cura 3D printers such as FDM, SLS, SLA
designed through computer aided ultimaker, slices the surfaces and then prints the product layer by
design (CAD) transfers to the 3D printer layer

Fig. 4. Steps Involved in A 3D Printed Dosage Form.

5926 | Int J Pharm Sci Nanotech Vol 15; Issue 2, March−April 2022

3D
PRINTER

Powder Extrusion based

Liquid solidification
solidification systems

Drop on drop Selective laser Drop on solid Fused deposition Pressure assisted
Stereolithography
deposition sintering deposition modelling syringe

Fig. 5. 3D Printing Technologies for Medicine Manufacture.

Ability to
create tablets
of any shape
and size

Ability to set
Ability to
the dosage
print small
individually
batches of
for each
drugs
patient
BENEFITS OF 3D
TECHNOLOGY IN
PHARMACEUTICAL
FIELD
Ability to
replace a
Eco-friendly
large number
production
of drugs with
one tablet
Ability to
control the
process of
release of
active
substances

Fig. 6. Benefits of 3D Technology in Pharmaceutical Field.

Mandloi et al: 3D Printing for Drug Delivery and its Pharmaceutical Applications – Recent Findings and Challenges | 5927

Absence of
Numerous Knowledge
Material
Absence of
Printing using
Industry
same Device
Particular
lead to
Overhaul

Restricted to
Minor
Global 3-D Printing
on Patent
Implementa-
Components
Challenges tion

Changing of
long
Adminstrative
Established
Consistence
Manufacturin
g Processes Hardware &
Expensive to
Function

Fig. 7. Global Challenges of 3D Printing Technology.

Unique
Dosage
Forms
Personalize
Drug
d Drug
Testing
Dosing

Medical Complex
Low cost of Applications Drug
Production of 3-D Release
printing Profile

Anatomical
Rapid Models for
Prototyping Surgical
Preprations
Bio-Printing
of Tissues
and Organs

Fig. 8. Applications of 3D Printing Technology.

5928 | Int J Pharm Sci Nanotech Vol 15; Issue 2, March−April 2022
3D printing is in its initial phase in the
pharmaceutical industry on the other hand it is more
advanced in the field of automobile, aerospace,
biomedical, and tissue engineering.
Main Components of a 3D Printer
The basic components of a 3D printer are-
(i) Print Bed (Tray): It is a type of flat surface where
the 3D models are layered at the time of printing.
Heated printed beds are used to avoid perverting
during the layering procedure.
(ii) Extruder: Extruder passes the plastic filament
inside the hot-end, which is its main function. It is
the plunge-out part. The binal extruder is used in
some types of printers, which the can print two
different materials at the same time.
(iii) Hot-end: Hot-end is formed due to the heat caused.
The filament is poured between the temperature
sensor and an extrusion edge for the deposition of
fused material. Printing accuracy depends upon the
nozzle size i.e., printing is more appropriate via a
smaller nozzle.
(iv) Filament: Similar to the inkjet ink, the 3D printer
is fed melted filament. It is used as the absorption
material (Mule et. al., 2020).
Types of 3D Printers
1. Fused Deposition Modeling (FDM): Fused
Deposition Modeling is based upon the principle of
extrusion of molten thermoplastics. It utilizes
thermoplastic polymers such as polyvinyl acetate
(PVA), Acrylonitrile butadiene styrene (ABS) in a
semi-molten form. Here, objects are built by
heating a thermoplastic filament to its melting
point and extruding the thermoplastic layer by
layer (Araújo et al., 2019; Cailleaux et al., 2021).
Advantages:
1. Printing cost is less and available extensively.
2. Plastic material is used hence it is cheaper.
3. There is no unbound loose powder.
4. There is no solvent removal required.
5. Friability and uniformity of drug are high.
Disadvantages:
1. Due to high-temperature deterioration of starting
material can happen.
2. The printing quality is not like those by SLA/SLS.
3. For support leave marks removal and sanding is
required.
4. Layer by layer printing might sometimes lead to a
problem with wrapping and minor shrinking
(Bhattacharya et al., 2019; Melocchi et al., 2020;
Mule et al., 2020; Wei et al., 2020; Vaz and
Kumar, 2021).
2. Stereolithography (SLA): Stereolithography uses
liquid plastic as the source material and this
liquid plastic material is transformed into a 3D
object, layer by layer. It uses a laser as the power
source. (Horst, 2018).
Advantages:
1. Speed
2. Suitable to all other types of 3D printing
technology, high accuracy as well as resolution.
3. Prototypes and designs made with
stereolithography are strong enough to be
machined.
Disadvantages:
1. Time-consuming.
2. Costly equipment.
3. Post-printing curing required (Mule et al., 2020;
Deshmane et al., 2021; Vaz and Kumar, 2021).
3. Selective Laser Sintering: It is similar to
stereolithography. However, Selective is based
upon the principle of laser-induced heating of
powder particles. (Mohapatra et al., 2022).
Advantages:
1. Easily reproducible and manageable.
2. Fastest process for printing functional durable,
prototypes or end-user parts.
3. Wide variety of materials with characteristics of
strength, durability, and functionality.
Disadvantages:
1. Requires post-printing finishing procedure.
2. Speed for interaction is restricted.
3. Due using of more energy inputs leads to
degradation starting materials (Vaz et. al.,2021;
Haris et. al.,2020; Mule et. al.,2020).
4. Inkjet Printing: Inkjet printing utilizes
electromagnet, heat, and piezoelectric technology
to force ‘ink’ onto a material, i.e., polymer powder
bed on the stage (Nandi, 2020; Thakur and
Murthy, 2021).
Advantages:
1. Simultaneous printing with multiple materials.
2. High resolution and smooth surface finish.
3. Printing over a large area.
Disadvantages:
1. Limited material selection.
2. Low part strength compared to bulk materials.
3. Substrate requirements (Vaz et. al.,2021; Haris
et. al.,2020; Mule et. al.,2020).
Different Methods Used in 3d Printing
Different methods used in 3D printing are mentioned in
Table 1.
Polymers Used in 3d Printing
Different polymers used in 3D printing are mentioned in
Table 2.
Mandloi et al: 3D Printing for Drug Delivery and its Pharmaceutical Applications – Recent Findings and Challenges | 5929

Table 1. Different Methods Used in 3D Printing. • Shows flexibility in formulation

S. Starting • Environment friendly (Jose and GV, 2018;
Method Principle References
No. Material Bakhatwar and Chikkala, 2019; Ali, Ahmad, and
Extrusion of
(Araújo et al., Akhtar, 2020; Abaci et al., 2021)
2019;
1. FDM Filament molten
Cailleaux
thermoplastics
et al., 2021) Disadvantages of 3D Printing
UV initiated • Scope for the manufacturing of illegal drugs
(Horst, 2018;
Liquid curing of
2. SLA
photopolymer defined photo
Deshmane • Regulatory concern
et al., 2021)
resin layers. • Violation of Copyrights
Laser induced (Vaz and • Low yield (Thakur and Murthy, 2021)
heating of Kumar, 2021; • Limited Size
3. SLS Powder
powder Mohapatra
particles. et al., 2022) • Limited Raw Materials (Ngo et al., 2018;
Drop on (Haris et al., Bhattacharya et al., 2019; Lamichhane et al.,
4. Inkjet Powder demand binder 2020; Mule 2019)
printing. et al., 2020)

Recent Researches of 3D Printing in the

Table 2. Polymers used in 3D Printing

Pharmaceutical Field
Polymer Drug Delivery System References

(Tagami et al.,
Poly vinyl alcohol
Tablets, Capsule 2017; Wei et al., In the past several years there have been several types of
(PVA)
2020)
research conducted in the pharmaceutical field for
(Chi et al., dosage forms such as, in the year 2019 Tagami et. al.
Polylactic acid (PLA) Nanofibers
2020) showed that the organic solvent type, temperature, and
(GV et al., 2017; drug concentration greatly affects the drug loading and
Polycaprolactone Tablets, carbon around 5% curcumin can be incorporated into the PVA
Ho
(PCL) nanotubes
et al., 2017) filament using the soaking method (Tagami et al., 2019).
Hydroxypropyl In the year 2020, Asmari et. al. conducted a study for the
(Cheng et al.,
methylcellulose Matrix tablets
2020) comparison of dissolution profiles using 3D printed PVA
(HPMC)
and commercial paracetamol tablets (Asmari, Sil, and
(Loureiro and Patel, 2020). In the year 2019 Wei et. al. performed a
Poly(lactic-co-glycolic Microsphere, capsules, Pereira, 2020;
acid) (PLGA) tablets, nanospheres Serris et al., study, in this study, the processability of PVA into melt-
2020) extruded filaments and then into 3D printed tablets by
(Beck et al., FDM was studied (Wei et al., 2020). In the year 2020,
Poly(methacrylate)
(Eudragit)
Nano capsules, Tablets 2017; dos Santos Macedo et. al. conducted a study and the aim was to
et al., 2021) evaluate the processability of PVA-based filaments
(Homaee containing paracetamol made by hot-melt extrusion for
Ethyl cellulose (EC) Tablets Borujeni
fused deposition modeling (Macedo et al., 2020).
et al., 2020)

(Borandeh et al.,
Polyurethane (PU) Tablets, Hydrogel
2021) Application of 3D Printing in the
Poly(methyl
methacrylate) Tablets
(Petersmann et Pharmaceutical Field
al., 2019)
(PMMA)
1. Rapid prototyping: It is used to create a real scale
Advantages of 3D Printing model of an object in a short lead time, using
Computer-Aided Design (CAD)
• High drug loading ability. 2. In the healthcare sector: Tools can be prepared for
• Cost reduction. surgery, medicines can be manufactured (Al-
• Customized and Personalized medication (Pandey Dulimi et al., 2021)
et al., 2020) 3. Reconstituting bones and body parts in forensic
• Accurate and precise dosing of potent drugs. pathology: Fingerprint examination, accident
• Enhanced productivity. reconstruction, structural, and industrial
accidents
• Treatment can be customized to improve patient
adherence, in the case of multidrug therapy with 4. Drug testing: It can fabricate complex geometries
multiple dosing regimens. to achieve various drugs releasing kinetics (Parhi,
2021)
• Suitable drug delivery for difficult to formulate
active ingredients.
5930 | Int J Pharm Sci Nanotech Vol 15; Issue 2, March−April 2022

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