Page 415 - IJB-10-5

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

1. Introduction with an earlier study of PEO for industrial applications
where thermoplastic processing was recommended to be
Polyethylene oxide (PEO) is a synthetic non-ionic carried out at temperatures below 130°. 11
hydrophilic polymer considered non-toxic in humans. It is
readily available in a wide range of molecular weights (M ) In contrast, high M PEOs (>1 M) displayed a
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up to 7 M. The M of the polymer used in the formulation reduction in M when processed in a single screw extruder
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can be selected to give a desired release profile with lower under elevated temperatures (100–170°) and short
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M typically used for rapid drug release since they dissolve residence time (2–3 min). In HME, PEO is subjected
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quickly in water. Conversely, the higher M PEOs (>0.3 M) to both mechanical and thermal stresses; thus, extruder
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are used in slow drug release systems. In these instances, configuration can impact the degradation process. In a
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the PEO is known to swell in water, forming a hydrogel layer recent study, formulations containing PEO (7 M) were
with increasing strength and thickness as M increases, processed in a twin screw extruder at 130°, which resulted
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thereby resulting in a slower drug release profile. 3,4 in significant degradation, leading to reduced viscosity
and accelerated drug release compared to unstressed
Polyethylene oxide (PEO) degradation has been 1
reported to occur at elevated temperatures in the presence formulations. Accordingly, another study indicated that
an increase in the M of PEO from 100 to 900 k delayed the
of oxygen through a scission of the chemical bond between drug release rate from HME extrudates as expected. Still,
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two carbon atoms, as well as the carbon-oxygen bonds, no significant extension in drug release time was achieved
giving smaller fragments. As a result, the M of PEO can by further increasing the M from 0.9 M up to 7 M. This
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decrease, which in turn reduces its viscosity. Additionally, can be interpreted as a sign of degradation of the high M
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the crystallinity of PEO is dependent on its thermal history; PEO (0.9–7 M) during extrusion. w
specifically cooling rapidly from above its melting point
(~70°) can result in a low level of crystallinity in the product, In practical terms, the high viscosity of molten high M
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which dramatically affects its solid-state properties. This PEO (≥0.9 M) can hinder its printability in fused deposition
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reduction in M and crystallinity during high-temperature modeling (FDM). Thus, a mixture of high M PEOs with
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processing, such as that encountered during hot melt other polymers can be used to reduce the melt viscosity
extrusion (HME), is known to increase the drug release and facilitate its printability. In this case, flexible polymers,
rates in formulated tablets. 1,3,7 Thus, it is challenging to such as low M polyethylene glycol (PEG), can protect PEO
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maintain the desired extended-release behavior of high M during extrusion and printing. 14,15 Given the potential for
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PEO (≥0.9 M) formulations when processed at elevated PEO application in controlled-release drug formulation
temperatures. Changes in M and crystallinity, and the designs, its complicated behavior under high-temperature
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resulting change in gelling behavior, are considered more processing conditions, and the limited study on the M
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pronounced when M of PEO is increased. For example, stability of 3D printed formulations containing PEO, the
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under the same storage conditions (40°), there was a more current study aimed to investigate (i) the impact of PEO M
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significant drop in the viscosity of PEO 7 M, hence a greater on its stability when mixed with other polymers; (ii) stability
increase in drug release rate, compared to PEO 4 M. 8,9 of PEO after dual thermal processing, i.e., HME followed
by FDM printing of tablets; and (iii) the impact of PEO
Based on thermogravimetric analysis (TGA) studies,
Vrandečić et al. found that the degradation of PEO occurs stability on physical properties and drug release from the
manufactured tablets. Two M of PEO (0.9 and 7 M) were
within the temperature range of 330–450°, independent of investigated under various processing conditions and in
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its M . It was also noted that the heating rate had a mixed combination with hydroxypropyl cellulose (HPC) and ethyl
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impact on degradation rates of low and high M PEOs; cellulose (EC). Since theophylline is a thermostable drug, it
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high M PEOs (1 and 5 M) degraded faster than low M was selected as the model drug for this study to minimize the
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PEOs (100 and 300 k) during rapid heating, while the effect of drug degradation on formulation characterization.
pattern is inverse during slow heating rate. Conversely, Tablets from thermal processes, such as HME and FDM,
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crystalline regions of PEO, which are more prevalent in were compared with milder, non-thermal processes, such as
high M PEO samples, appear to have better resistance to direct compression of a physical mixture of powders.
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degradation than amorphous regions. This may explain
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the lower stability of low M PEOs compared with high M 2. Materials and methods
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PEOs. Despite the aforementioned potential liabilities,
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PEO has been successfully processed by thermal methods 2.1. Materials
(HME and injection molding [IM]) for drug delivery. For Theophylline anhydrous (purity: >99%) was purchased
example, low M PEOs (<300 k) exhibit good stability from Fisher Scientific (United Kingdom, UK) and used
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under temperatures as high as 140° during IM, consistent as a model drug with a high melting point around 273°.
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Volume 10 Issue 5 (2024) 407 doi: 10.36922/ijb.4055