Paracetamol extended release FDM 3D printlets: Evaluation of formulation variables on printability and drug release

Đuranović, Marija; Obeid, Samiha; Madžarević, Marijana; Cvijić, Sandra; Ibrić, Svetlana

doi:10.1016/j.ijpharm.2020.120053

Cited by 34 publications

(15 citation statements)

References 40 publications

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“…In this procedure, the drug loaded filament is manufactured by hot melt extrusion to later be fed into the 3D printer and be heated again. For example, Ðuranović et al [26] processed paracetamol loaded filaments based on poly(ε-caprolactone) (PCL) and poly ether oxide (PEO) polymers. They succeeded in extruding filaments and printing with drug loads up to 48% wt at 130 • C but their polymer-drug blends underwent two thermal processes, and although the processing temperature was under the melting point of the paracetamol, their samples showed yellowish discoloration, indicating some degradation or oxidation of the components.…”

Section: Introductionmentioning

confidence: 99%

Direct Powder Extrusion of Paracetamol Loaded Mixtures for 3D Printed Pharmaceutics for Personalized Medicine via Low Temperature Thermal Processing

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Tena

Duque³

et al. 2021

Pharmaceutics

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Three-dimensional printed drug development is nowadays an active area in the pharmaceutical industry, where the search for an appropriate edible carrier that permits the thermal processing of the mixture at temperature levels that are safe for the drug is an important field of study. Here, potato starch and hydroxypropyl cellulose based mixtures loaded with paracetamol up to 50% in weight were processed by hot melt extrusion at 85 °C to test their suitability to be thermally processed. The extruded mixtures were tested by liquid chromatography to analyze their release curves and were thermally characterized. The drug recovery was observed to be highly dependent on the initial moisture level of the mixture, the samples being prepared with an addition of water at a ratio of 3% in weight proportional to the starch amount, highly soluble and easy to extrude. The release curves showed a slow and steady drug liberation compared to a commercially available paracetamol tablet, reaching the 100% of recovery at 60 min. The samples aged for 6 weeks showed slower drug release curves compared to fresh samples, this effect being attributable to the loss of moisture. The paracetamol loaded mixture in powder form was used to print pills with different sizes and geometries in a fused deposition modelling three-dimensional printer modified with a commercially available powder extrusion head, showing the potential of this formulation for use in personalized medicine.

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Section: Introductionmentioning

confidence: 99%

Direct Powder Extrusion of Paracetamol Loaded Mixtures for 3D Printed Pharmaceutics for Personalized Medicine via Low Temperature Thermal Processing

Mendibil

Tena

Duque³

et al. 2021

Pharmaceutics

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“…Two different approaches can be considered to apply dose personalization: (i) changing the amount of active ingredient in the filament and (ii) modifying the project by changing the dimensions or infill density of the tablet. Although the production of low-dose dosage forms does not cause many difficulties, an increase of the API content is usually associated with a significant decrease in printability; several works reporting the possibility of printing from filaments containing even 50–60% ( w / w ) of the API have been recently published [ 36 , 37 , 38 ]. Sadia et al printed tablets using filaments containing from 2.5% to 50% w / w of hydrochlorothiazide using Eudragit PO with addition of triethyl acetate and tricalcium phosphate.…”

Section: Introductionmentioning

confidence: 99%

“…Among the formulations containing 60% of API, only filament based on PCL and made from PEO 200 K with the addition of Gelucire ® 44/14 were printable. The authors also noted that printing with high drug-loaded filaments is difficult due to the clogging of the printer nozzle [ 37 ]. The 3DP prolonged-release tablets containing theophylline and metformin were reported by Verstraete et al As filament-forming polymers, they used hydrophilic and hydrophobic thermoplastic urethanes containing 20%, 40%, or 60% of API, respectively.…”

Section: Introductionmentioning

confidence: 99%

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

et al. 2021

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The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.

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“…Decision trees are powerful classification algorithms that are used in medicine and other areas [30,[33][34][35]. Decision trees have been also used to analyze the printability of filaments in the FDM technique [36] but there is no literature data on the application of decision tree methodology in SLS printing. Created decision trees can be used for predicting printability instead of usage in a trial-and-error approach, which is both time-and resource-consuming.…”

Section: Decision Treementioning

confidence: 99%

Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model

et al. 2021

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Selective laser sintering (SLS) is a rapid prototyping technique for the production of three-dimensional objects through selectively sintering powder-based layer materials. The aim of the study was to investigate the effect of energy density (ED) and formulation factors on the printability and characteristics of SLS irbesartan tablets. The correlation between formulation factors, ED, and printability was obtained using a decision tree model with an accuracy of 80%. FT-IR results revealed that there was no interaction between irbesartan and the applied excipients. DSC results indicated that irbesartan was present in an amorphous form in printed tablets. ED had a significant influence on tablets’ physical, mechanical, and morphological characteristics. Adding lactose monohydrate enabled faster drug release while reducing the possibility for printing with different laser speeds. However, formulations with crospovidone were printable with a wider range of laser speeds. The adjustment of formulation and process parameters enabled the production of SLS tablets with hydroxypropyl methylcellulose with complete release in less than 30 min. The results suggest that a decision tree could be a useful tool for predicting the printability of pharmaceutical formulations. Tailoring the characteristics of SLS irbesartan tablets by ED is possible; however, it needs to be governed by the composition of the whole formulation.

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Paracetamol extended release FDM 3D printlets: Evaluation of formulation variables on printability and drug release

Cited by 34 publications

References 40 publications

Direct Powder Extrusion of Paracetamol Loaded Mixtures for 3D Printed Pharmaceutics for Personalized Medicine via Low Temperature Thermal Processing

Direct Powder Extrusion of Paracetamol Loaded Mixtures for 3D Printed Pharmaceutics for Personalized Medicine via Low Temperature Thermal Processing

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model

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