Page 416 - IJB-10-5

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

Low-viscosity HPC (M : ~95 k; Kucel EF) was provided compressed into a tablet of 333.3 mg with a hydraulic
TM
w
by Ashland Inc. (Netherlands). Dibutyl sebacate (DBS) manual tableting press (Model MTCM-I; Globe Pharma,
was supplied by Sigma-Aldrich (United States of America USA), equipped with 10 mm diameter concave punches.
[USA]). EC (M : ~23 k, Ethocel 10 FP) and PEO (M : 7 M, The employed pressure was 150 bar, and the dwell time was
w
w
POLYOX WSR 303; and M : 0.9 M, POLYOX WSR 1105) constant at 10 s.
w
were obtained from Colorcon Ltd. (UK) as a gift.
2.3.2. Hot-melt extrudate tablets
2.2. Formulation development The physical admixture was fed manually at (an average
Preliminary observation revealed that formulations solely of) 1 g/min into a 10-mm twin-screw extruder L/D 20
containing PEO and theophylline were not printable because (assembled by Point1 Controls/R Controls; Stoke-on-Trent,
of the high melt viscosity of PEO (M : 0.9 and 7 M). Therefore, UK) at a screw speed of 50 rpm. The temperature of the
w
a mixture with other polymers was needed to produce feed zone was set at 130°, and the temperature for the rest
printable PEO formulations (Table 1). Since the study focuses of the zones (including the die) was set at 140°. Although
on the thermal stability of PEO, thermally stable polymers this temperature exceeds the melting temperature (T ) of
m
(HPC and EC) were selected to be mixed with PEO. PEO (73°), it was necessary to exceed the glass transition
16
Theophylline percentage was kept constant (30% [w/w]) in temperature (T ) of HPC and EC mixed with PEO.
g
all the developed formulations (see compositions in Table 1). Additionally, PEO was processed at high temperatures
In formulations containing EC (F and F ), a plasticizer above its T to investigate (i) the impact of temperature and
3
4
m
(DBS) was also added to improve printability and reduce the compare the results with other similar studies 12,15,17 and (ii)
brittleness of EC. DBS was added to EC powder at 13% (w/w) the effect of thermal process conditions on PEO stability
of EC weight (equivalent to 5.2% of the total formulation), and drug release. Filaments were collected manually using
mixed thoroughly, and left overnight for better sorption of the a winder. After collecting and cooling, the filaments were
liquid plasticizer to the EC chains. Thereafter, the plasticized cut manually into small pieces around 2 mm in length
EC was ready to use in making formulations F and F . using a pair of scissors. Then, 5 g of the resulting samples
4
3
All studied formulations (F –F ) were prepared into were transferred to a ball mill (PM 100; Retsch GmbH,
1
4
tablets by three distinct methods: direct compression Germany) and ground for 4 min at 400 rpm. The ground
of the physical mixture (PM), compression of HME powders were collected from the ball mill and kept in tightly
extrudates, and 3D printing. All tablets were then studied closed containers at room temperature. The powders were
for dissolution and other physical characteristics. compressed into tablets using a hydraulic manual tableting
press (Model MTCM-I; Globe Pharma, USA) equipped
2.3. Tablet preparation with 10 mm diameter concave punches. Compression was
Tablets were prepared via three different methods: direct carried out at 150 bar with a 10-s dwell time. The nominal
compression of PM, compression of powders prepared weight of each tablet was 333.3 mg, equivalent to 100 mg
from HME, and 3D printing of HME filaments (via FDM). of theophylline.
The manufactured tablets were stored in enclosed vials in
a chamber at room temperature (22 ± 2°) and tested for 2.3.3. Printed tablets
dissolution within a week. Filaments were prepared using HME, as mentioned earlier.
The diameter of the filaments is crucial as the filaments
2.3.1. Physical mixture tablets should fit into the feeding nozzle of the FDM printer,
Using the formulation compositions mentioned in which has a diameter of 1.75 mm. The diameter of the
Table 1, the powders were mixed using mortar and filaments was measured using a vernier caliper, and only
pestle (approximately for 5 min). The powder blend was filaments with a diameter ranging between 1.7 and 1.8

Table 1. Composition of studied formulations.

Formulation Composition (%)
Theophylline PEO (7 M) PEO (0.9 M) HPC EC DBS
F 30 30 — 40 — —
1
F 30 — 30 40 — —
2
F 3 30 30 — — 40 5.2
F 4 30 — 30 — 40 5.2
Abbreviations: PEO: Polyethylene oxide; HPC: Hydroxypropyl cellulose; EC: Ethyl cellulose; DBS: Dibutyl sebacate.

Volume 10 Issue 5 (2024) 408 doi: 10.36922/ijb.4055