Screening of pharmaceutical polymers for extrusion-Based Additive Manufacturing of patient-tailored tablets

Samaro, Aseel; Janssens, Peter; Vanhoorne, Valérie; Renterghem, J. Van; Eeckhout, Mia; Cardon, Ludwig; Beer, Thomas De

doi:10.1016/j.ijpharm.2020.119591

Cited by 49 publications

(34 citation statements)

References 34 publications

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“…Stress (14.0, 13.0 and 9.7 MPa) and strain at break (4.3, 2.4 and 2.3%) diminished together with the tensile energy to break the filament (36.0, 13.8 and 11.9 × 10

J/m

) for the 0, 1 and 10% drug-loaded filaments, respectively. This is consistent with literature findings where, e.g., the addition of metoprolol tartrate (crystalline) in general reduced the mechanical properties [ 34 ]. The drug is expected to remain crystalline within the polymer matrix based on the mechanical data, Arrhenius activation energy of flow and processing temperature (160

), which is below the melting point of ZHT (

).…”

Section: Resultssupporting

confidence: 93%

“…Qualitative caplets were printed with a nozzle temperature of 160

and bed temperature of 55

for the placebo and drug-loaded blends. In general, when a crystalline filler or API is added to the blend, the printing temperature needs to be increased [ 34 ]. This printing temperature was previously linked to the Arrhenius flow activation energy (Ea) of the matrix system.…”

Section: Resultsmentioning

confidence: 99%

“…The roller was necessary due to die swelling, which is an increase of the filament diameter upon leaving the die. Die swell occurs due to relaxation of the polymers after exposure to high stress within the extruder and die, and the extent depends on HME parameters and intrinsic polymer properties [ 34 ]. Filaments with a diameter outside the acceptable range for printing were discarded.…”

Section: Methodsmentioning

confidence: 99%

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Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy

Henry¹,

Vadder²,

Decorte³

et al. 2021

Pharmaceutics

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The long-term use of benzodiazepine receptor agonists (BZRAs) is associated with multiple side effects, such as increased sedation, hangover or an elevated risk of dependency and abuse. Unfortunately, the long-term use of BZRAs is reaching worrying intake rates, and therefore, the need for action is high. It was demonstrated already that the overall willingness of patients for deprescription increased when a slow dose reduction scheme with the possibility for dose increase, if needed, is employed. The current study aims to develop a flexible dosing platform of zolpidem hemitartrate (ZHT) to facilitate such withdrawal therapy. As this is the first report on the extrusion and 3D printing of ZHT, its thermal behaviour and sensitivity towards photolytic degradation was characterised. It was shown that ZHT possesses multiple polymorphs and was especially prone to oxidative photolysis. Next, a variety of immediate release polymers (Eudragit EPO, Kollidon VA64, Kollidon 12PF and Soluplus) were blended and extruded with Polyox WSR N10 to investigate their feedability and printability by mechanical and rheological analysis. The addition of PEO was shown to enable printing of these brittle pharmaceutical polymers, although the processing temperature was deemed critical to avoid surface defects on the resulting filaments. An EPO(70)PEO(30) system was selected based on its suitable mechanical properties and low hygroscopicity favoring ZHT stability. The matrix was blended with 1% or 10% API. The effect of certain printing parameters (caplet size, nozzle diameter, % overlap) on dissolution behaviour and caplet weight/dimensions/quality was assessed. A flexible dosing platform capable of delivering <1 mg and up to 10 mg of ZHT was created. Either caplet modification (incorporation of channels) or disintegrant addition (Primojel, Explotab, Ac-Di-Sol, Primellose and Polyplasdone-XL) failed to achieve an immediate release profile. This study provides the first report of a 3D-printed flexible dosing platform containing ZHT to aid in withdrawal therapy.

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“…Stress (14.0, 13.0 and 9.7 MPa) and strain at break (4.3, 2.4 and 2.3%) diminished together with the tensile energy to break the filament (36.0, 13.8 and 11.9 × 10

J/m

), which is below the melting point of ZHT (

).…”

Section: Resultssupporting

confidence: 93%

“…Qualitative caplets were printed with a nozzle temperature of 160

and bed temperature of 55

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy

Henry¹,

Vadder²,

Decorte³

et al. 2021

Pharmaceutics

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show abstract

“…For example, a tablet printed with HPC-L instead of HPC-SL based on the same in silico model gave a diameter increase from 9.8 to 10.4 mm [34]. In another study, smaller dimensions compared to the theoretical ones were reported for a variety of materials [37,54]. The influence of process settings on these dimension is less known and, therefore, investigated in-depth in the following section.…”

Section: Dimensional Analysismentioning

confidence: 98%

“…The effects of infill and overlap are evident since more material is printed. Many studies have already indicated that infill has a significant influence on the weight [26,32,33,43,54].…”

Section: Weightmentioning

confidence: 99%

Influence of Print Settings on the Critical Quality Attributes of Extrusion-Based 3D-Printed Caplets: A Quality-by-Design Approach

et al. 2021

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Extrusion-based 3D-printing is an easy-to-use, cheap manufacturing technique that could be used to produce tailored precision medicines. The technique has an almost unlimited versatility since a multitude of print parameters can easily be adapted. Unfortunately, little is known of the effect of these print parameters on the critical quality attributes of the resulting printlets. In this study, practical guidelines and means to adapt certain parameters in order to achieve the desired outcome (e.g., acceptable visual quality and flexible dosing) are stipulated for medical 3D-printing using a design-of-experiments approach. The current study aims at elucidating the effect of five print parameters (infill, overlap, number of shells, layer height and layer pattern) on the mechanical properties, dimensions, weight, porosity and dissolution characteristics of a fixed-size caplet consisting of Eudragit EPO (69.3%), Polyox WSR N10 (29.7%) and zolpidem hemitartrate (1%). In terms of the mechanical properties, 3D-printed caplets possessed anisotropy where the vertical compression strength and Brinell hardness exceeded the diametral strength. In general, all 3D-printed caplets possessed acceptable mechanical strength except for a small region of the knowledge space. Dimensional analysis revealed small, statistical significant differences between different runs, although the clinical relevance of this variation is likely negligible. The weight or dose of a caplet can be varied mainly using the infill and overlap and, to a lesser extent, via the layer height and number of shells. The impact on porosity was complicated as this was influenced by many factors and their interactions. Infill was the only statistically relevant factor influencing the dissolution rate of the current formulation. This study unravels the importance of the print parameter overlap, which is a regularly neglected parameter. We also discovered that small dose variations while maintaining the same dissolution profile were possible via modifying the overlap or number of shells. However, large dose variations without affecting the dissolution behaviour could only be accomplished by size modifications of the printlet.

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Analytical Characterisation of 3D‐Printed Medicines

Lima,

Sá‐Barreto,

Cunha‐Filho

2024

3D Printing of Pharmaceutical and Drug Delivery Devices

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Screening of pharmaceutical polymers for extrusion-Based Additive Manufacturing of patient-tailored tablets

Cited by 49 publications

References 34 publications

Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy

Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy

Influence of Print Settings on the Critical Quality Attributes of Extrusion-Based 3D-Printed Caplets: A Quality-by-Design Approach

Analytical Characterisation of 3D‐Printed Medicines

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