Hot-Melt Extrusion Process Fluctuations and Their Impact on Critical Quality Attributes of Filaments and 3D-Printed Dosage Forms

Abstract

Fused deposition modeling (FDMTM) is a 3D-printing technology of rising interest for the manufacturing of customizable solid dosage forms. The coupling of hot-melt extrusion with FDMTM is favored to allow the production of pharma-grade filaments for the printing of medicines. Filament diameter consistency is a quality of great importance to ensure printability and content uniformity of 3D-printed drug delivery systems. A systematical process analysis referring to filament diameter variations has not been described in the literature. The presented study aimed at a process setup optimization and rational process analysis for filament fabrication related to influencing parameters on diameter inhomogeneity. In addition, the impact of diameter variation on the critical quality attributes of filaments (mechanical properties) and uniformity of mass of printed drug-free dosage forms was investigated. Process optimization by implementing a winder with a special haul-off unit was necessary to obtain reliable filament diameters. Subsequently, the optimized setup was used for conduction of rational extrusion analysis. The results revealed that an increased screw speed led to diameter fluctuations with a decisive influence on the mechanical resilience of filaments and mass uniformity of printed dosage forms. The specific feed load was identified as a key parameter for filament diameter consistency.

Polyvinyl Alcohol-Based 3D Printed Tablets: Novel Insight into the Influence of Polymer Particle Size on Filament Preparation and Drug Release Performance

“…Filament diameter uniformity is fundamental as variations affect the mechanical properties. Thin sections tend to fracture more rapidly than thicker ones [ 50 ], frequently leading to filament breakage inside the print head and disruption of the printing process. It also impacts the uniformity of mass of the 3D printed drug delivery systems, since in FDM the average diameter of the filament is applied for the determination of the feed rate in the G-code.…”

Multivariate Design of 3D Printed Immediate-Release Tablets with Liquid Crystal-Forming Drug—Itraconazole

“…The obtained itraconazole-loaded filaments were opaque and creamy in color. The diameter of the filaments was kept at a constant level; however, in the case of the PVA_K/CL filament, the diameter variations were higher than 0.05 mm, which is considered as a maximum acceptable deviation from the declared diameter [71]. The itraconazole content and its uniformity were satisfactory.…”

Predicting Drug Release from 3D Printed Oral Medicines Based on the Surface Area to Volume Ratio of Tablet Geometry

“…In fused deposition modeling (FDM) 3D printing, intermediates containing the API, so-called filaments, are produced by hot-melt extrusion [ 3 , 16 , 17 , 18 ]. Filaments have to meet certain mechanical properties in order to enable the subsequent printing process [ 16 , 19 , 20 ].…”