Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments

Filaments loaded with griseofulvin (GF), a model poorly water-soluble drug, were prepared and used for 3D printing via fused deposition modeling (FDM). GF was selected due to its high melting temperature, enabling lower temperature hot-melt extrusion (HME) keeping GF largely crystalline in the filam...

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Autores principales:	Guluzar Gorkem Buyukgoz, Christopher Gordon Kossor, Rajesh N. Davé
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	FDM 3D printing amorphous solid dispersions (ASDs) tablet design tablet surface area drug supersaturation release kinetics Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/5a8bf4a5b9e844099a534933b982c644
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id	oai:doaj.org-article:5a8bf4a5b9e844099a534933b982c644
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spelling	oai:doaj.org-article:5a8bf4a5b9e844099a534933b982c6442021-11-25T18:41:12ZEnhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments10.3390/pharmaceutics131118571999-4923https://doaj.org/article/5a8bf4a5b9e844099a534933b982c6442021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1857https://doaj.org/toc/1999-4923Filaments loaded with griseofulvin (GF), a model poorly water-soluble drug, were prepared and used for 3D printing via fused deposition modeling (FDM). GF was selected due to its high melting temperature, enabling lower temperature hot-melt extrusion (HME) keeping GF largely crystalline in the filaments, which could help mitigate the disadvantages of high HME processing temperatures such as filament quality, important for printability and the adverse effects of GF recrystallization on tablet properties. Novel aspects include single-step fusion-assisted ASDs generation during FDM 3D printing and examining the impact of tablet surface areas (SA) through printing multi-mini and square-pattern perforated tablets to further enhance drug supersaturation during dissolution. Kollicoat protect and hydroxypropyl cellulose were selected due to their low miscibility with GF, necessary to produce crystalline filaments. The drug solid-state was assessed via XRPD, DSC and FT-IR. At 165 °C HME processing temperature, the filaments containing ~80% crystalline GF were printable. Fusion-assisted 3D printing led to GF supersaturation of ~153% for cylindrical tablets and ~293% with the square-pattern perforated tablets, indicating strong monotonous impact of tablet SA. Dissolution kinetics of drug release profiles indicated Fickian transport for tablets with higher SA, demonstrating greater SA-induced drug supersaturation for well-designed 3D printed tablets.Guluzar Gorkem BuyukgozChristopher Gordon KossorRajesh N. DavéMDPI AGarticleFDM 3D printingamorphous solid dispersions (ASDs)tablet designtablet surface areadrug supersaturationrelease kineticsPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1857, p 1857 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FDM 3D printing amorphous solid dispersions (ASDs) tablet design tablet surface area drug supersaturation release kinetics Pharmacy and materia medica RS1-441
spellingShingle	FDM 3D printing amorphous solid dispersions (ASDs) tablet design tablet surface area drug supersaturation release kinetics Pharmacy and materia medica RS1-441 Guluzar Gorkem Buyukgoz Christopher Gordon Kossor Rajesh N. Davé Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments
description	Filaments loaded with griseofulvin (GF), a model poorly water-soluble drug, were prepared and used for 3D printing via fused deposition modeling (FDM). GF was selected due to its high melting temperature, enabling lower temperature hot-melt extrusion (HME) keeping GF largely crystalline in the filaments, which could help mitigate the disadvantages of high HME processing temperatures such as filament quality, important for printability and the adverse effects of GF recrystallization on tablet properties. Novel aspects include single-step fusion-assisted ASDs generation during FDM 3D printing and examining the impact of tablet surface areas (SA) through printing multi-mini and square-pattern perforated tablets to further enhance drug supersaturation during dissolution. Kollicoat protect and hydroxypropyl cellulose were selected due to their low miscibility with GF, necessary to produce crystalline filaments. The drug solid-state was assessed via XRPD, DSC and FT-IR. At 165 °C HME processing temperature, the filaments containing ~80% crystalline GF were printable. Fusion-assisted 3D printing led to GF supersaturation of ~153% for cylindrical tablets and ~293% with the square-pattern perforated tablets, indicating strong monotonous impact of tablet SA. Dissolution kinetics of drug release profiles indicated Fickian transport for tablets with higher SA, demonstrating greater SA-induced drug supersaturation for well-designed 3D printed tablets.
format	article
author	Guluzar Gorkem Buyukgoz Christopher Gordon Kossor Rajesh N. Davé
author_facet	Guluzar Gorkem Buyukgoz Christopher Gordon Kossor Rajesh N. Davé
author_sort	Guluzar Gorkem Buyukgoz
title	Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments
title_short	Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments
title_full	Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments
title_fullStr	Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments
title_full_unstemmed	Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments
title_sort	enhanced supersaturation via fusion-assisted amorphization during fdm 3d printing of crystalline poorly soluble drug loaded filaments
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5a8bf4a5b9e844099a534933b982c644
work_keys_str_mv	AT guluzargorkembuyukgoz enhancedsupersaturationviafusionassistedamorphizationduringfdm3dprintingofcrystallinepoorlysolubledrugloadedfilaments AT christophergordonkossor enhancedsupersaturationviafusionassistedamorphizationduringfdm3dprintingofcrystallinepoorlysolubledrugloadedfilaments AT rajeshndave enhancedsupersaturationviafusionassistedamorphizationduringfdm3dprintingofcrystallinepoorlysolubledrugloadedfilaments
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Enhanced Supersaturation via Fusion-Assisted Amorphization during FDM 3D Printing of Crystalline Poorly Soluble Drug Loaded Filaments

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