Development of immediate release 3D-printed dosage forms for a poorly water-soluble drug by fused deposition modeling. Study of morphology, solid state and dissolution
Authors
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Publication date
15.04.2021
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Type
01A - Journal article
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Parent work
International Journal of Pharmaceutics
Special issue
DOI of the original publication
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Series
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Volume
599
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Publisher / Publishing institution
Elsevier
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Abstract
3D-printing technologies such as Fused Deposition Modeling (FDM) bring a unique opportunity for personalized and flexible near-patient production of pharmaceuticals, potentially improving safety and efficacy for some medications. However, FDM-printed tablets often exhibit tendency for slow dissolution due to polymer erosion-based dissolution mechanisms. Development of immediate release (IR) 3D-printed dosage with poorly water-soluble compounds is even more challenging but necessary to ensure wide applicability of the technology within pharmaceutical development portfolios. In this work, process and morphology were considered to achieve IR of BCS class IV compound lumefantrine as model active pharmaceutical ingredient (API) using basic butylated methacrylate copolymer (Eudragit EPO) as matrix former, as well as hydrophilic plasticizer xylitol and pore former maltodextrin. Grid-designed tablets with size acceptable for children from 6 years old and varying programmed infill density were successfully 3D-printed with 5% lumefantrine while higher drug load led to increased brittleness which is incompatible with 3D-printing. Lumefantrine assay was 92 to 97.5% of theoretical content depending on drug load and process parameters. 3D-printed tablets with 65% infill density met rapid release criteria, while 80% and 100% showed slower dissolution. Structural characteristics of 3D-printed tablets with non-continuous surface such as accessible porosity and specific surface area by weight and by volume were quantified by a non-destructive automated µCT-based methodology and were found to correlate with dissolution rate. Increase in accessible porosity, total surface area, specific surface area and decrease in relative density were statistically significant critical factors for modification of lumefantrine dissolution rate. Crystallinity in manufactured tablets and filaments was explored by highly sensitive Raman mapping technique. Lumefantrine was present in the fully amorphous state in the tablets exhibiting adequate stability for on-site manufacturing. The study demonstrates feasibility of immediate release FDM-3D-printed tablets with BCS class IV API and illustrates the correlation of FDM design parameters with morphological and dissolution characteristics of manufactured tablets.
Keywords
3D-printing, Tablet Immediate release, Poorly soluble drug, X-ray computer microtomography, Personalized dosage form, BCS class IV drug
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ISBN
ISSN
0378-5173
1873-3476
1873-3476
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Gold
License
Citation
IMANIDIS, Georgios, Marina FANOUS, Malak BITAR, Sarah GOLD, Adam SOBCZUK, Adam HIRSCH und Joerg OGORKA, 2021. Development of immediate release 3D-printed dosage forms for a poorly water-soluble drug by fused deposition modeling. Study of morphology, solid state and dissolution. International Journal of Pharmaceutics. 15 April 2021. Bd. 599. DOI 10.1016/j.ijpharm.2021.120417. Verfügbar unter: https://doi.org/10.26041/fhnw-4105