European Journal of Pharmaceutical Sciences 135 (2019) 60–67

Contents lists available at ScienceDirect

European Journal of Pharmaceutical Sciences

journal homepage: www.elsevier.com/locate/ejps

Digital light processing (DLP) 3D-printing technology and photoreactive T

polymers in fabrication of modified-release tablets
⁎
Hossam Kadrya,b, Soham Wadnapc, Changxue Xuc, Fakhrul Ahsana,
a
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Dr., Amarillo, TX 79106, United States of
America
b
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt
c
Department of Industrial, Manufacturing, and Systems Engineering, Texas Tech University, Lubbock, TX 79409-3061, United States of America

A R T I C LE I N FO A B S T R A C T

Keywords: In this study, we assessed the feasibility of using digital light processing (DLP) 3D printers (3DP) in fabrication of
3D printing solid oral dosage forms. The DLP technology uses a digital micromirror device (DMD) that reflects and focuses
PEGDA ultraviolet (UV) light on the surfaces of photoreactive materials that polymerize in a layer-by-layer fashion.
PEGDMA Using poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) dimethacrylate (PEGDMA) as pho-
Drug release
toreactive polymers and theophylline as a model drug, we deployed a DLP printer to fabricate tablets. After
Digital micromirror device (DMD)
Photoreactive polymers
optimizing various printing parameters including UV intensity and exposure time, layer thickness, and polymer
concentration, we printed various types of tablets with and without perforation. We then assessed the tablets for
drug content, mechanical strengths, swellability, weight variation, microscopic features, drug-polymer inter-
actions and drug release profiles. The loading of theophylline was 1%, which was independent of tablet weights.
The drug content and weight variation were within the acceptable range, as recommended by the United States
Pharmacopeia (USP). Scanning electronic microscopic (SEM) pictures showed tablets with distinct layers and
smooth outer surfaces. The spectral scans, obtained using Fourier Transform Infrared Spectroscopy (FTIR),
showed no chemical interactions between the drug and polymers. Similarly, drug content determined using a UV
spectrophotometer was the same as that determined by a high performance liquid chromatography (UPLC). The
extent of drug release increased with the increase in the number of perforations in the tablets. Overall, this study
demonstrates that DLP 3DP can be used as a platform for fabricating oral tablets with well-defined shapes and
different release profiles.

1. Introduction
Current studies concerning the application of 3DP technologies in
fabrication of pharmaceutical dosage forms revolve around three major
areas including (i) use of new printers or technologies (Clark et al.,
2017; Fina et al., 2017; Khaled et al., 2014; Wang et al., 2016), (ii)
exploration of new feeding materials (Okwuosa et al., 2016; Sadia et al.,
2016; Zhang et al., 2017), and (iii) optimization of established methods
for fabrication of tablets with better resolution (Gioumouxouzis et al.,
2017; Goyanes et al., 2015b; Kadry et al., 2018). Other applications of
3DP include fabrication of microfluidic devices, printing of cell-laden
organs and many non-medical objects (Kimlinger and Martin, 2018; Liu
et al., 2018). More specifically, 3DP technologies that have thus far
been used in designing and fabrication of pharmaceutical dosage forms
include binder deposition techniques, bioprinters, fused deposition
modeling, and stereolithography (Goyanes et al., 2015a; Katstra et al.,
2000; Khaled et al., 2015; Wang et al., 2016). In binder deposition
technology, inkjet printers are used to add drops of binders over a layer
of powder that causes powder particles to adhere and form a predefined
2D shape. On the first layer of powder, a series of powder layers is
added, and the process is continued until a 3D shape develops (Rowe
et al., 2000). First FDA approved 3DP tablet, Spritam®, was fabricated
using this technique. However, tablets prepared with binder deposition
techniques suffer from poor resolution and inadequate mechanical
strength. On the other hand, bioprinters have been used to prepare oral
tablets containing one or more drug substances. In bioprinters, a paste
of drug-polymer mixture is extruded via the printer nozzle, the ex-
truded pastes then grow into a given shape, and then the final semisolid
objects undergo a drying step (Khaled et al., 2014). However, this
technique requires additional post-processing steps such as drying and
heating for solidification.
The fused deposition modeling (FDM) technology, on the other

⁎
Corresponding author at: 1300 Coulter Dr., Amarillo, TX 79106, United States of America.
E-mail address: fakhrul.ahsan@ttuhsc.edu (F. Ahsan).

https://doi.org/10.1016/j.ejps.2019.05.008
Received 14 September 2018; Received in revised form 18 April 2019; Accepted 12 May 2019
Available online 17 May 2019
0928-0987/ © 2019 Elsevier B.V. All rights reserved.
H. Kadry, et al.
hand, uses filaments that move through the print head, softens the fi-
laments by heating and prints objects in a layer-by-layer fashion
(Goyanes et al., 2014). The low cost, ease of operation and the avail-
ability of a wide variety of feeding materials have generated much in-
terest in using FDM printers for fabrication of pharmaceutical products.
Further, FDM printers can be integrated with a hot melt extruder for
preparing filaments and printing tablets. The FDM technology allows
fabrication of tablets with adequate mechanical strengths and lends the
flexibility in preparing tablets with customized drug release profiles just
by varying the infill density, tablet geometry, or arrangement of drug-
free versus drug-loaded layers (Goyanes et al., 2014; Goyanes et al.,
2015b; Kadry et al., 2018; Okwuosa et al., 2017). However, this tech-
nology requires elevated temperature for preparation of filaments and
printing of tablets and thus is currently used for printing of only ther-
mostable materials. Although using a proper combination of feeding
materials, FDM printers can be operated at low temperatures and used
in printing of thermolabile drugs (Kollamaram et al., 2018), these
printers still require heat to prepare filaments and print tablets.
Crosslinkable photopolymers have been used as feeding materials to
overcome the limitations of printing of solid drug products containing
thermolabile drug substance (Clark et al., 2017; Wang et al., 2016).
Because of no involvement of heat and ease of preparation of drug-
laden photopolymers, improved resolution, photo-polymerization
based techniques have attracted much interest in the fabrication of oral
solid dosage forms. Technologies that use photopolymers as feeding
materials include inkjet and stereolithography (SLA). In the inkjet
technology, photoreactive polymers are jetted via a printer nozzle,
cured with a light emitting diode (LED) UV lamp, cured polymeric
drops deposit in successive two-dimensional images over multiple
layers to form 3D objects (Clark et al., 2017). In the SLA technology, a
single UV laser beam moves along the surface of photoresins in a row by
row fashion that results in localized polymerization and solidification.
Solidification is repeated in a layer by layer manner until a solid 3D
object emerges (Arcaute et al., 2010; Melchels et al., 2010).
The stereolithography has been modified by incorporating a digital
micromirror device (DMD) in the optical path of the laser, which
eliminates the need for scanning and thus allows creating a complete
layer in a single exposure (Lu et al., 2006). DMD consists of thousands
of moving micromirrors that switch between on and off positions. Based
on the loaded images, this technology let light reflect in a defined
pattern, via an optical system, and strike the surface of a resin and cause
solidification of the desired region. Although originally developed for
the display industry, DMD technology, known as digital light processing
(DLP) technology, have been used in many other areas including wa-
velength multiplexing (McConnell et al., 2006), hyperspectral imaging
(Gibson et al., 2013), and computational imaging (Sun et al., 2013).
Compared with laser-based SLA printers, DLP printers are faster, more
efficient, and allow operating at a wide range of wavelengths. Unlike
laser-based commercially available SLA printers, which do not offer the
flexibility of using very small amount of resins for printing, DLP printers
are adaptable to customized resin reservoirs and small volumes of
photoreactive polymers.
Despite the promise of DLP 3DP in printing medical devices and
microneedle-mediated drug delivery systems (Bloomquist et al., 2018;
Lim et al., 2017), this technology has not yet been deployed in fabri-
cation of solid oral dosage forms. As such, for the first time, here we
seek to assess the feasibility of deploying DLP 3DP in fabrication of solid
oral dosage forms. Using theophylline as a model drug and two
common photoreactive polymers, PEGDA and PEGDMA, we varied the
polymer concentration to produce sturdy tablets with minimum
polymer concentration. With a goal to achieve different drug release
profiles, we also designed and prepared tablets with varying surface
areas. In addition, we assessed the interactions between the drug and
photopolymers using FTIR spectroscopy.
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European Journal of Pharmaceutical Sciences 135 (2019) 60–67
2. Materials and methods
2.1. Materials
Theophylline was purchased from Acros Organics (Pittsburgh, PA).
Poly(ethylene gycol)(n) diacrylate (PEGDA 400) and Polyethylene
glycol dimethacrylate (PEGDMA 1000) were purchased from
Polysciences, Inc. (Warrington, PA) and the photoinitiator, 2-Hydroxy-
4′-(2-hydroxyethoxy)-2-methylpropiophenone, was purchased from TCI
America (Portland, OR). The salts used in preparing dissolution media
were purchased from Sigma-Aldrich Inc. (St Louis, MO).
2.2. Preparation of photopolymer solution
We used PEGDA and PEGDMA as the primary polymers to prepare
the photoreactive solution. Dissolving 100 mg of theophylline in deio-
nized water, we added 0.5–2 mL (5–20%, v/v) of PEGDA or PEGDMA
and vortexed for 1 min. Next, we added the photoinitiator to the mix-
ture at a concentration of 0.5% (w/v) and adjusted the final volume
with deionized water to 10 mL and vortexed the solution for the pho-
toinitiator to completely dissolve. The final solution, which contained
80% water and 20% drug-polymer mixture, was kept in light-resistant
containers at ambient temperature.
2.3. Tablets fabrication and processing parameters
Using a digital light processing 3DP, DLP® Discovery™ 4100 (Dallas,
TX) equipped with Omnicure s2000 (Excelitas Technologies Corp.,
Waltham, MA) as a UV source, we printed the tablets for this study.
First we created CAD files for tablets using SolidWorks™ software
(Dassault Systèmes, France) and saved the file as stereolithography files
(.stl). Then using a slicing software, we sliced STL files into multiple
sections, each corresponding to a single layer, and finally saved the files
as printer readable JPEG files. An optical element was used to gather
and focus the reflected UV light onto the resin reservoir (Fig. 1). The
JPEG pictures were black and white (Fig. 2A), as any white color gave
instructions to the micro-mirrors to be activated and reflect UV light
and vice versa. Tablets were printed at room temperature with a fixed
dimension of 7.5 mm long × 5.4 mm wide × 4 mm height, and a layer
thickness of 200 μm. We printed the tablets at various printing condi-
tions by changing UV exposure time and intensity, and polymer con-
centration (Table 1). After printing, we stored the tablets in air-tight
containers and thus to prevent any shrinkage due to loss of water.
2.4. Physical characterization
2.4.1. FTIR analysis
Using a Bruker Optics VERTEX 70 FT-IR spectrometer (Billerica,
MA), we conducted spectroscopic analysis of PEGDA, PEGDMA, theo-
phylline, and printed tablets. All samples were scanned between 4000
and 600 cm−1 at 4 cm−1 resolution, and 64 scans using the Platinum
ATR (Attenuated Total Reflectance) diamond crystal accessory.
2.4.2. Scanning electron microscopy (SEM)
Using a Hitachi S-3400N scanning electron microscope (Hitachi
High-Tech Science Corporation, Japan) and a SESI detector, we ex-
amined the surface morphology of the printed tablets at 5 kV accel-
erating voltage under high vacuum. Prior to imaging, samples were
freeze-dried to remove the water, then placed on a metallic stub, and
finally coated with a thin layer of Au/Pd for better conductivity.
2.5. Evaluation of tablet hardness, swelling ratio and water content
2.5.1. Tablet hardness
The fracture strength, defined as the force required to break a tablet
by radial compression, was measured using a conventional tablet
H. Kadry, et al. European Journal of Pharmaceutical Sciences 135 (2019) 60–67

Fig. 1. A schematic diagram of the Digital Micromirror Device (DMD) stereolithography setup.

Fig. 2. Design and images of 3D printed theophylline tablets: (A) Design of three types of tablets containing no holes, two or six holes. (B and C) Pictures showing the
top and tilted views of 3DP tablets without perforation and those with two or six holes. (D) Images of tablets printed using opaque PEGDA and transparent PEGDMA.

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Table 1 samples using the above UV spectrophotometric method and the drug
Optimization of tablet printing parameters and tablet properties. concentration was obtained from a standard curve. By plotting % drug
Polymer concentration UV intensity Exposure time Printability released against time, we graphed the release profiles of the tablets.
(%) (mW/cm2) (s) Data are reported as mean ± standard deviation. Using a model in-
dependent method to quantify time-dependent change in drug release
5 6 25 Soft
(Ruiz and Volonté, 2016), we calculated the dissolution efficiency (DE)
5 6 35 Soft
∫t1t 2 % Dt . dt AUC
5 12 25 Soft using the following equation: DE = ·100 = ⎡ % D 0 −TT ⎤·100 .
% Dmax (t2 − t 1 )
5 12 35 Soft ⎣ max ⎦
Here %Dt is percentage dissolved at time t, %Dmax the maximum dis-
10 6 25 Easily break
10 6 35 Easily break solved at the final time point T, AUC0-T is the area under the curve from
10 12 25 Easily break 0 to T. After calculating AUC and DE, we compared the DEs using one-
10 12 35 Breakable way ANOVA.
20 6 25 Not well defined shape
20 6 35 Not well defined shape
20 12 25 Not well defined shape 3. Results and discussion
20 12 35 Adequate
3.1. Tablet fabrication and processing parameters

hardness tester (Tianjin Gouming Medicinal Equipment Co. LTD.,
Tianjin, China) (n = 3).
2.5.2. Determination of swelling ratio
We determined the swelling ratio, defined as the ratio of the weight
of the tablets after swelling to that of before swelling, to assess the
propensity of the tablets to imbibe water. For this assessment, soon
after printing the tablets, we removed uncured resins from the tablet
surfaces using a piece of filter paper and weigh the tablets (n = 3),
denoted as Wi, which was the weight of tablet dry tablets. We then
placed the tablets in a beaker containing deionized water for 24 h, re-
moved the tablets from the beaker, wipe the tablets to remove excess
water, recorded the weight of the tablets, denoted as Ws, which was
considered as weight of swelled tablets. Finally, we calculated the
swelling ratio (SR) using the following equation: SR = Ws Wi .
2.5.3. Water content
To determine the water content, we first took the weight (Wi) of
freshly prepared tablets (n = 3), placed them in a 60 °C oven for 24 h
for the tablets to dry completely and then again took the weight of the
tablets (Wd). Finally, we calculated the water content (WC) using the
( )
following equation: WC = Wi − Wd Wi × 100 .
2.6. Determination of drug content and dissolution profiles
We determined the drug content using both UV spectroscopy and
ultra-performance liquid chromatography (UPLC). For both methods,
we crushed the tablets using a mortar and pestle, transferred the cru-
shed tablets into a 100 mL volumetric flask, and then diluted with PBS.
After sonicating the samples for 30 min, stirring overnight at room
temperature (Clark et al., 2017), we aliquoted the samples. For UV
spectroscopic determination of the drug content, we read the samples at
270 nm in a UV/VIS 918 Spectrophotometer (GBC Scientific Equipment
LLC., Hampshire, IL). For chromatographic analysis, we used a Waters
Acquity UPLC chromatographic system (Waters Corp., Milford, MA)
and C18 column (100 × 2.1 mm, 1.7 μm; Waters, Dublin, Ireland). The
mobile phase for the validated UPLC system was made of 0.05 M am-
monium acetate (90%) and acetonitrile (10%), which was flowed at
0.3 mL/min at room temperature and eluent was read at 270 nm.
Following a United States Pharmacopeia (USP) recommended pro-
tocol for theophylline tablets (USP, 2015), we conducted the dissolution
assay. Using a USP II dissolution apparatus (Vankel 7000 Dissolution
Testing Station, Vankel Technology Group, Cary, NC), we placed one
tablet in each dissolution vessel containing 100 mL PBS (n = 3). Setting
the paddle speed at 50 rpm and maintaining the vessel temperature at
37 ± 0.5 °C, we collected 1 mL sample at various time points (0, 5, 15,
and 30 min, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 h). The volume of the
samples collected each time was replaced with an equivalent amount of
PBS to maintain the sink condition. Theophylline was measured in the
In this study, we used for the first time a DLP printer for fabricating
solid oral dosage forms using photoreactive polymers. This printer of-
fers fast and efficient printing because it can convert 2D images into 3D
objects by projecting the light onto a whole layer at once, while SLA or
laser-based printers print each layer in a line by line fashion. Further,
the UV intensity, exposure time, resin volume and reservoir size can be
modified in DLP printers and the resolution of the printers can be as
high as 10 μm. Varying the concentration of photopolymers, UV in-
tensity and exposure time (time to print), we tested the assumption that
printing conditions influence physical and release properties of the ta-
blets. True to our assumption, various printing conditions, including
polymer concentrations and UV intensity and exposure time had major
influence on the printability of tablets (Table 1). In order to identify the
optimal polymer concentration, we started with a minimal concentra-
tion of the photopolymers. When we used 5% polymer, the resulting
tablets were too soft to handle and to maintain their shape. Similarly,
when the polymer concentration was 10% and the drug-polymer mix-
ture was exposed to a UV intensity of 6 mW/cm2 at 25 s/layer, there
was not much improvement in the printability and tabletability of the
drug polymer mixture. Keeping the polymer concentration at 10%,
when we increased UV intensity and exposure time to 12 mW/cm2 and
35 s/layer, respectively, printed tablets even then failed to maintain the
desired shape or underwent deformation. However, increasing photo-
polymer concentration to 20% and setting UV intensity and exposure
time at 12 mW/cm2 and 35 s/layer, respectively, we obtained tablets
with adequate mechanical strength, which can be crushed using a
conventional hardness tester as discussed below (Table 3). The ex-
posure time used in this study was relatively longer because the con-
centration of the polymer was low. However exposure can be reduced
by increasing the concentration or type of the photopolymer, which was
not feasible in this study because our model drug, theophylline, had
poor loading efficiency for the PEG-based polymer, a limitation of this
study. Overall, this optimization study suggests that the concentration
of photopolymer and UV intensity/exposure time play important role in
the printability of tablets using DLP printers.
3.2. Physical characterization and drug content
Two photopolymers produced tablets with varying degrees of pe-
netrability to the room light (Fig. 2B–D). Tablets prepared using
PEGDMA were translucent, similar to the solution of photoreactive
polymers before crosslinking. On the other hand, tablets made of
PEGDA were opaque, although the polymer solution was translucent
before printing. This change in the optical property of the tablets may
have resulted from the crosslinking and subsequent changes in the re-
fractive index of printed tablets (Zhang et al., 2018). Three different
sets of tablets were prepared for each photopolymer: Intact non-per-
forated tablets and tablets with 2 or 6 perforations (Fig. 2C). The drug
loading in each tablet was 1% (w/w) because of the high water

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H. Kadry, et al.
Table 2
Drug content and weight uniformity of different 3D printed tablets.
Tablets Drug content1 Drug content2 Weight uniformity
(% ± SD) (% ± SD) (mg ± SD)
20% PEGDMA Non- 97.18 ± 0.81 97.30 ± 0.97 165.73 ± 1.43
perforated
2 holes 97.74 ± 0.31 98.78 ± 0.24 151.93 ± 2.75
6 holes 98.10 ± 0.30 98.20 ± 0.35 133.70 ± 0.79
20% PEGDA Non- 98.75 ± 0.96 98.38 ± 0.55 174.23 ± 2.25
perforated
2 holes 98.57 ± 1.37 98.62 ± 1.12 160.70 ± 2.69
6 holes 97.85 ± 1.21 97.55 ± 0.62 155.27 ± 2.78
Determined by 1UV spectrophotometer and 2ultra-performance liquid chro-
matography.
solubility of theophylline. Based on the tablet weight, the drug content
in the printed tablets were 1.3 to 1.7 mg per tablet and weight of the
tablets was between 133.70 mg and 174.23 mg (Table 2), which was
97.18–98.75% of the initial amount of the drug mixed with the
polymer. Also, there was no significant differences between the drug
content that was determined by UPLC versus UV spectrophotometer. In
fact, the retention time in UPLC for the drug did not change upon
crosslinking. The spectrum for the solution of dissolved tablets showed
a small peak, which was distinct from the theophylline peak and might
belong to the small amount of polymer or photoinitiator that leached
from the tablets into the solution. This result suggests that no drug
underwent degradation during printing and theophylline was stable at
the used UV intensity and duration. In fact, publish studies also suggest
that theophylline had no stability problems when exposed to UV light
(Kim and Tanaka, 2009). The weight variation for each set of tablets
(Table 2) was less than 5%, complying with the USP specifications
(USP, 2015). When stored in tightly closed containers at ambient
temperature, tablets did not dry or shrink, an indication that tablets are
likely to maintain their shape in the room environment.
The digital pictures and SEM photographs showed smooth upper
surface of the tablets, suggesting printing of one layer followed by
successive layers (Fig. 3B). SEM pictures show the additive character-
istics or layer-by-layer features of 3D printing, each layer being 200 μm
thick, similar to the patterns in masonry walls (Fig. 3A). The smooth
outer surface and glass-like inner surface of the perforated part of the
tablets indicate the superior capability of DLP printers for printing ta-
blets with uniform weights and dimensions (Fig. 3C).
3.3. FTIR
The IR spectra for PEGDA, PEGDMA, theophylline powder and ta-
blets prepared by mixing theophylline with either PEGDA or PEGDMA
are presented in Fig. 4. The FTIR profiles help assess the presence of the
drug substance within the printed tablets, the compatibility between
theophylline and photopolymers, and the degree of curing of tablets.
The spectrum of crystalline theophylline powder showed characteristic
peaks at 3120 cm−1 (NeH stretching), 1710 cm−1 (C]O stretching of
ketone), 1664 cm−1 (C]C stretching), 1564 cm−1 (C]N stretching),
and 1317 cm−1 (CeO stretching) (Kumar Singh Yadav and Shivakumar,
2012; Sekharan et al., 2011). The distinctive peaks of theophylline,
with only subtle differences, were present in the IR spectra of the tablets
prepared with PEGDA or PEGDMA, suggesting no interactions between
theophylline and the photoreactive polymers. To confirm the poly-
merization of PEGDMA and PEGDA after UV curing, we compared the
IR spectra of the photopolymers before and after UV treatment. The
uncured PEGDA and PEGDMA spectra had characteristic peaks at
2870 cm−1 (methylene stretching), 1722 cm−1 (C]O stretching) and
1637 cm−1 (acrylate C]C stretching) (Clark et al., 2017; Hwang et al.,
2015). After the UV treatment, the peaks at 1637 cm−1 disappeared
because of the conversion of C]C bonds to CeC bonds, which
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European Journal of Pharmaceutical Sciences 135 (2019) 60–67
contribute to the crosslinking (Killion et al., 2012; Lin and Lee, 2003).
The FTIR spectrum, which is often considered as the fingerprint of a
given chemical compound, suggest that the photopolymers acted as
inert materials when combined with theophylline or exposed to UV-
light induced crosslinking and as such the spectrum of the drug remain
unaltered.
3.4. In vitro release profiles
By assessing the dissolution profiles of the tablets, we determined
the influence of polymers and tablet design, non-perforated versus
perforated tablets, on drug release profiles. The volume of the dis-
solution medium was 100 mL, unlike the USP recommended volume of
900 mL for studying the dissolution of drug products containing
200–400 mg drug. The rationale for choosing 100 mL dissolution
medium was that our test products, i.e. tablets, contained 1–2 mg drug.
As such, similar to the USP recommended method, the sink condition
was maintained for studying the dissolution of our 3DP tablets. In fact,
when the drug amount in an experimental dosage form is smaller than
that in a commercial drug product, the volume of the dissolution media
are often reduced to a smaller volume (Lobenberg et al., 2000;
Phanapavudhikul et al., 2008).
The data presented in Fig. 5, suggest that the intact non-perforated
tablets of PEGDMA produced maximum release in 6 h and that 65%
drug was released within an hour. Intact tablets prepared using PEGDA
showed the same release patterns, but drug release was maximum after
8 h (Fig. 5A). To increase the surface area and thus to enhance the re-
lease rate, we printed tablets containing 2 and 6 perforations. Tablets
made of either polymers with 2 holes showed the same release patterns;
≅98% drug was released in 3 h (Fig. 5B). However, PEGDMA-tablets
containing 6 holes produced 100% drug release in 1.5 h and PEGDA-
tablets showed 97% release in 3 h (Fig. 5C), suggesting that PEGDMA
would be better suited for immediate release tablets. Dissolution effi-
ciency (DE) data (Fig. 5D), a model independent approach that gives
information concerning the extent of drug release in a given period,
suggest that polymer type, PEGDMA versus PEGDA, and presence or
absence of holes and number of holes influences the drug release pro-
files. PEGDMA-tablets and presence of six holes produced much faster
and pronounced drug release than PEGDA-tablets.
In biomedical research, photoreactive polymers such as PEGDMA
and PEGDA have been investigated extensively, especially for their
various applications in tissue engineering and drug delivery (Lin-Gibson
et al., 2004; Martinez et al., 2017). Because they are available in dif-
ferent molecular weights and are biocompatible, poly(ethylene glycol)
diacrylate (PEGDA) and poly(ethylene glycol) dimethacrylate
(PEGDMA) have been widely studied for their potential application in
fabrication of 3DP drug products too. These acrylated PEGs can be used
in fabrication of drug products upon optimizing different factors such as
UV intensity, exposure time, polymer molecular weight, and the con-
centration of photoinitiator (Sabnis et al., 2009). Recently, PEGDAs
have been used to prepare sustained release ocular implants, which
were safe to retinal epithelial cells (McAvoy et al., 2018).
The drug release from tablets prepared using two PEG-based pho-
topolymers may have occurred via diffusion of the drug through the gel
layer produced around the tablets due to penetration of water into the
tablets. Because the tablets contained about 80% entrapped water, the
release of drug from the tablets was much faster (Table 3) unlike tablets
that had no entrapped water, as reported in a previous publication
(Martinez et al., 2017). In fact, the rate and extent of drug dissolution
can vary depending on the water content (Martinez et al., 2017). The
extent of cross linking in a given polymer can also affect the release
pattern. Because of the presence of two -CH3 (methacrylate) sub-
stituents, the scaffold of PEGDMA is reported to have a denser cross-
linked network and thus stronger steric constraint compared with that
of PEGDA (Kalakkunnath et al., 2006). As such, the higher water con-
tent and different levels of crosslinking density are perhaps the reasons
H. Kadry, et al. European Journal of Pharmaceutical Sciences 135 (2019) 60–67

Fig. 3. SEM images of (A) Intact non-perforated tablets showing the layer-by-layer structure, (B) Top surface of intact non-perforated tablets, (C) Top view of printed
holes showing the inner surface.

for the differences in the release rates from the tablets prepared with
PEGDMA versus those prepared with PEGDA. The presence of a rela-
tively higher amount of water in either polymer perhaps played no roles
in drug release from PEGDMA versus PEGDA because there was no
increase in the swelling ratio when tablets were incubated in water for
24 h (Table 3). Unlike other tablets prepared with biodegradable
polymers, which are known to release drugs via polymer erosion and
dissolution (Fina et al., 2017; Goyanes et al., 2014; Kadry et al., 2018;
Sadia et al., 2016), tablets made of cross-linkable photoreactive poly-
mers, such as PEGDA and PEGDMA, remained intact throughout the
dissolution test (Clark et al., 2017) due to the formation of a gel layer
surrounding the tablets. Similar to a published study (Martinez et al.,
2018), here we have also demonstrated that DLP 3D printers can be
used to print tablets with varying surface area and thus can fabricate
tablets with distinct release profiles.
Taken together, this study suggests that DLP 3DP can be used for

Fig. 4. FTIR spectra of the formulation components and theophylline tablets prepared with (A) PEGDMA and (B) PEGDA.

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H. Kadry, et al. European Journal of Pharmaceutical Sciences 135 (2019) 60–67

Fig. 5. Drug release profiles of 3D printed tablets: (A) Intact non-perforated tablets. (B) 3D tablets with 2 holes. (C) 3D tablets with 6 holes. (D) Dissolution efficiency
AUC
(DE), calculated using the following equation: ⎡ % D 0 − TT ⎤ ·100 . Please see the text for details on DE calculation. * compared with intact PEGDMA (p =); # compared
⎣ max ⎦
with intact PEGDA (p =); ψ compared with 6 holes PEGDMA (p =); χ compared with 2 holes PEGDA (p =); ϕ compared with 6 holes PEGDMA (p =).

Table 3 4. Conclusions
Hardness, water content, and swelling ratio of different 3D printed tablets.
Tablets Hardness Water content Swelling ratio In this study, we used a DLP 3D printer, for the first time, to produce
(N) (%) solid oral dosage forms. Unlike other UV based 3D printers, this tech-
nique lends the flexibility to customize various printing parameters
20% PEGDMA Non-perforated 3.54 ± 0.87 78.50 ± 0.84 1.05 ± 0.06 such as UV intensity, exposure time, even UV light source, wavelength,
2 holes 2.20 ± 0.10 77.93 ± 1.02 1.05 ± 0.06
6 holes 1.13 ± 0.06 75.01 ± 1.28 1.10 ± 0.01
and amounts of polymers. Further, photoreactive polymer preparation
20% PEGDA Non-perforated 3.07 ± 0.40 77.03 ± 1.12 1.05 ± 0.01 and printing can be performed at room temperature and thus tech-
2 holes 2.00 ± 0.70 78.62 ± 0.90 1.05 ± 1.01 nology can be used for the production of solid oral dosage forms of a
6 holes 1.30 ± 0.20 78.49 ± 0.79 1.09 ± 0.04 wide selection of thermostable and thermo-labile drugs. This tech-
nology will allow fabrication of tablets with distinct release properties
such as immediate and extended release tablets.
printing both thermostable and thermolabile drugs because unlike
other technologies such as FDM, this technology uses no heat at all
Acknowledgements
during the printing process. However, this 3DP technology is not
without its limitations because the solubility of the drugs in the polymer
This study is supported by a TTUHSC internal fund. We thank Dr.
and stability of drug under UV light may restrict deploying this method
Taslim Al-Hilal for his help in correcting English of parts of the
for printing drug products. Drug loading, for example, for theophylline
manuscript and his enthusiastic discussion concerning the deployment
was rather poor although the drug was soluble in the polymers and thus
of 3DP in fabrication of pharmaceutical dosage forms.
for deploying this technology, drugs should be carefully selected. Other
concerns would be the safety of the photopolymers although PEG based
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