Production of Reproducible Filament Batches for the Fabrication of 3D Printed Oral Forms

Abstract

Patients need medications at a dosage suited to their physiological characteristics. Three-dimensional printing (3DP) technology by fused-filament fabrication (FFF) is a solution for manufacturing medication on demand. The aim of this work was to identify important parameters for the production of reproducible filament batches used by 3DP for oral formulations. Amiodarone hydrochloride, an antiarrhythmic and insoluble drug, was chosen as a model drug because of dosage adaptation need in children. Polyethylene oxide (PEO) filaments containing amiodarone hydrochloride were produced by hot-melt extrusion (HME). Different formulation storage conditions were investigated. For all formulations, the physical form of the drug following HME and fused-deposition modeling (FDM) 3D-printing processes were assessed using thermal analysis and X-ray powder diffraction (XRPD). Filament mechanical properties, linear mass density and surface roughness, were investigated by, respectively, 3-point bending, weighing, and scanning electron microscopy (SEM). Analysis results showed that the formulation storage condition before HME-modified filament linear mass density and, therefore, the oral forms masses from a batch to another. To obtain constant filament apparent density, it has been shown that a constant and reproducible drying condition is required to produce oral forms with constant mass.

Keywords: 3D printing; filament; fused-filament fabrication; hot-melt extrusion; immediate release; oral forms; pediatric.

Figure 1

3 points bending setup with attached filament.

Figure 2

X-ray powder diffraction analysis of amiodarone hydrochloride formulations (green), amiodarone hydrochloride (black), PEO (blue), d-sorbitol (red).

Figure 3

Thermal degradation profile of powders formulations before production.

Figure 4

Amiodarone powder formulation dynamic vapor sorption (DVS) isotherm plot, sorption in red and desorption in blue.

Figure 5

Differential scanning calorimeter (DSC) thermograms of amiodarone hydrochloride, polyethylene oxide (PEO), d-sorbitol and powders formulation (A) and particle size analysis dry dispersion method (PSD) graphs of the batches (B).

Figure 6

SEM micrographs with ×100 magnification of amiodarone formulations free powders after storage. From the top corner left to the bottom right are presented batches DR1, DR2, DR3, NDR1, NDR2 and DR4.

Figure 7

Thermal analysis and X-ray powder diffraction of PEO-based filaments. (A) Thermal degradation profile, (B) DSC thermograms of the six filaments batches and (C) X-ray powder diffraction spectra of the six filaments batches (green), PEO (purple), amiodarone hydrochloride (black) and d-sorbitol (red).

Figure 8

Amiodarone hydrochloride filaments under binocular microscope ×6.

Figure 9

Raman mapping of the slice of a DR2 filament with the representative spectra of the individual compounds at the bottom (yellow: d-sorbitol; blue: amiodarone hydrochloride; red: PEO). Raman mapping is at the top with the same color code indicating the relative presence of the components of the filament with (A) all components, (B) d-sorbitol, (C) amiodarone hydrochloride, (D) PEO.

Figure 10

Load-deflection profiles of filament samples in tensile tests.

Figure 11

Photo of the three printed oral forms (from left to right, 51 mm, 100 mm and 200 mm filaments).

Figure 12

Thermal analysis and X-ray powder diffraction of PEO-based oral forms. (A) Thermal degradation profile, (B) DSC thermograms of the six oral forms batches and (C) X-ray powder diffraction spectra of the six oral forms batches (green), PEO (blue), amiodarone hydrochloride (black) and d-sorbitol (red).

Figure 13

Oral form weights as a function of the filament quantity used by the 3D-printing process (top) and corresponding mass RSD (bottom).

Figure 14

Photo of oral amiodarone forms showing different shapes and sizes.