An investigation into drug content uniformity in fused filament fabrication

Brammer, Elanor and Halbert, Gavin and Lamprou, Dimitrios (2016) An investigation into drug content uniformity in fused filament fabrication. In: 2016 AAPS Annual meeting and exposition, 2016-11-13 - 2016-11-17, Colorado Convention Center. (Unpublished) (http://abstracts.aaps.org/Verify/AAPS2016/PosterSu...)

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Abstract

Purpose With the recent FDA approval of the first 3D printed tablet, there seems to be a gradual shift towards new methods for manufacturing dosage forms. 3D printing has the potential to provide a huge level of flexibility in dosing, leading towards a much more personalised care package for the patient. Fused filament fabrication is a 3D printing technique which uses an extruded polymer strand as feedstock. This strand can be loaded with a drug either during, or after, the extrusion process, allowing for various concentrations of active pharmaceutical ingredient (API) within the polymer. As with any manufacturing technique, it is essential that a high level of control is maintained throughout the manufacturing process, and a good indication of this control is a homogeneous drug distribution throughout the polymer matrix. Methods Drug loading was carried out post-extrusion, by submerging the filament in a methanolic solution of the API for 24 hours. After drying in a vacuum oven, subsequent printing was carried out using a Creatr HS 3D Printer, manufactured by Leapfrog. For investigation into the drug loading of printer filaments, a combination of surface and internal analysis was carried out. For visualisation of the drug distribution on the surface of the filament, both atomic force microscopy (AFM) and time of flight secondary ion mass spectrometry (TOF-SIMS) were utilised. For analysis of the internal drug distribution, TOF-SIMS was again used, but was limited by the depth it could penetrate from the surface. The Bruker Skyscan 2211 is an X-ray nanotomograph (nano-CT) and can analyse both the surface and the internal structure of a sample, allowing for a complete picture to be built up. Results AFM shows a difference in adhesion across a section of the filament surface allowing differentiation between areas of high and low drug loading. This uneven distribution is also observed with TOF-SIMS analysis, which allows a map of a surface to be created, showing areas corresponding to the mass ion of the API (Figure 1). TOF-SIMS can also create a 3D map of this same area by carrying out depth profiling. This shows that the majority of the drug is located on the surface of the filament, with additional deposits randomly spaced deeper in the internal structure (Figure 2). Analysis of the printed tablet with nano-CT shows differences in density across the internal structure and suggests the API is well distributed after printing, but further analysis is required. Conclusions These results illustrate the drug distribution obtained within both a filament and a tablet, using the post-extrusion method of drug loading. At present, there is little control over the drug loading process, leading to a non-homogeneous distribution of API within the polymer filament. The tablet appears to have a more even distribution compared with the filament, but further analysis is required to accurately determine location of API. Future work will involve investigation into in situ drug loading during the extrusion process, in the hope that a homogeneous drug distribution can be achieved.

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