Page 417 - IJB-10-5

International Journal of Bioprinting Stability of 3D-printed PEO tablets

mm were selected for printing tablets. The computer-aided with a refractive index detector. Samples for GPC were
design (CAD) model of a cylindrical tablet was designed prepared in 1 mg/mL solutions by dissolving formulation
online using Tinker CAD and then exported as an STL file, powders in dimethyl formamide (DMF) containing 5
which was imported to the software Makerbot Replicator mM NH BF and 0.25/100 mL of toluene at 40° for 30
4
4
2X printer (Makerbot Inc., USA). Printed tablets had a min. In-house experiments revealed that samples were
height of 4.5 mm and a diameter of 9.5 mm. Based on the not dissolved by stirring over 24 h at room temperature
preliminary experiments, those dimensions were selected (25 ± 2°). Thus, heating was essential to achieve complete
(i) to get the same tablet weights as those prepared by solubility when preparing the samples. Thereafter, 100 µL
other methods (333.3 mg) and (ii) to get a similar surface of the sample was injected into a PLgel 5 μm guard column
area (SA)/volume (V) ratio as other tablets (0.8 mm ). (50 × 7.5 mm), followed by two PLgel 5 μm MIXED-D
−1
This enables a more accurate comparison, as weight and (300 × 7.5 mm) columns at 60°. The mobile phase was
SA/V can have an impact on drug release profiles. Printing DMF containing 5 mM NH BF at a flow rate of 1 mL/
4
4
settings were as follows: layer height: 0.2 mm; infill density: min. Despite the protocol being developed in-house, it is
100%; number of shells: 2; printing speed: 90 mm/s; bed relatively similar to other protocols where DMF and gentle
temperature: 50°; and nozzle temperature: 220°. heating were used with PEO samples. 18,19
2.4. Differential scanning calorimetry As the aim was to find the impact of different
The solid-state and thermal behavior of raw materials and processing conditions on PEO M , a comparative study
w
formulations was investigated using differential scanning was conducted without using a reference standard. In
calorimetry (DSC) 4000 system (Perkin Elmer, USA). brief, GPC experiments were conducted with PEO in its
It was used to determine the T and T of EC and HPC, pure form and in formulations processed via three distinct
g
m
as well as the T of PEO, theophylline, and each of the methods (PM, HME at 150°, and FDM at 220°). After the
m
formulations. Approximately 6 mg of each material or GPC test, all obtained chromatographs were compared
formulation was placed into crucible aluminum pans, and against each other (a comparative study).
samples were scanned from 25 to 300°, encompassing the 2.7. Particle size analysis of ground filaments
high temperatures used in HME and printing methods. Particle size distribution was measured manually using a
The samples were scanned at a scanning rate of 10°/min nest of five small sieves with different aperture sizes (63,
with nitrogen purging at a flow rate of 20 mL/min. The 150, 250, 600, and 2000 µm). Sieving time was 3 min,
obtained DSC traces were analyzed using Pyris software where sieves were agitated in linear and circular motions
(Perkin Elmer, USA).
with repeated tapping. The sample weight was around 2
2.5. X-ray powder diffraction g. The starting weight of the sample was recorded and the
To investigate the effect of extrusion and 3D printing on the weight of powder retained on each sieve after the sieving
crystallinity of the formulations, X-ray powder diffraction test was also recorded and converted to % of mass retained
(XRPD) patterns of theophylline, PEO, EC, HPC, PM on each sieve (frequency%). Size distribution was plotted
tablets, HME tablets, and FDM tablets were determined based on the retained mass % against the aperture size of
using a Siemens D500 X-ray diffractometer (Siemens, the sieve. The average size (A) was calculated based on the
Germany) with copper radiofrequency (Rf) radiation at 40 retained mass % (w ) in each sieve and sieve diameter (d),
i
i
kV voltage and 30 mA. Data were recorded at 2θ of 5–50° as presented in Equation I: 20
at a step width of 0.01° and 1 s time count. XRPD samples
are preferably in powder form, which was possible for
PM and HME samples. However, 3D-printed tablets were ∑ w × d i
i
too hard to grind; thus, thin films were printed, followed A= ∑ w (I)
by manual grinding using a pestle and mortar to achieve i
finer samples. Peak intensity is an arbitrary factor in this
study since tested samples were varied in their weight 2.8. Tablet characteristics
and particle size; thus, diffractograms were compared for Tablets were characterized in terms of their weight,
any changes in peak shape, position, and broadening to SA/V ratio, hardness, and porosity. True density was also
assess crystallinity. measured using a helium pycnometer (AccuPyc II 1340;
Micromeritics, USA) since the thermal process can alter
2.6. Gel permeation chromatography the true density of the material, as reported in previous
Gel permeation chromatography (GPC) was run in work. The density of physical mixture powders, ground
16
a 1260 Infinity GPC system (Agilent, UK) equipped filaments, and ground printlets were considered the true

Volume 10 Issue 5 (2024) 409 doi: 10.36922/ijb.4055