An investigation into drug content uniformity in fused filament fabrication

Elanor Brammer, Gavin Halbert, Dimitrios Lamprou

Research output: Contribution to conferencePoster

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.

Conference

Conference2016 AAPS Annual meeting and exposition
CountryUnited States
CityDenver
Period13/11/1617/11/16
Internet address

Fingerprint

Pharmaceutical Preparations
Secondary Ion Mass Spectrometry
Tablets
Polymers
Printing
Pharmaceutical Solutions
Atomic Force Microscopy
Drug and Narcotic Control
Dosage Forms
Vacuum
Patient Care
X-Rays
Ions
Three Dimensional Printing

Keywords

  • fused filament fabrication (FFF)
  • 3D Printing
  • drug delivery
  • pharmaceutical manufacturing

Cite this

Brammer, E., Halbert, G., & Lamprou, D. (2016). An investigation into drug content uniformity in fused filament fabrication. Poster session presented at 2016 AAPS Annual meeting and exposition, Denver, United States.
Brammer, Elanor ; Halbert, Gavin ; Lamprou, Dimitrios. / An investigation into drug content uniformity in fused filament fabrication. Poster session presented at 2016 AAPS Annual meeting and exposition, Denver, United States.1 p.
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abstract = "PurposeWith 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.MethodsDrug 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.ResultsAFM 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. ConclusionsThese 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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author = "Elanor Brammer and Gavin Halbert and Dimitrios Lamprou",
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note = "2016 AAPS Annual meeting and exposition ; Conference date: 13-11-2016 Through 17-11-2016",
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Brammer, E, Halbert, G & Lamprou, D 2016, 'An investigation into drug content uniformity in fused filament fabrication' 2016 AAPS Annual meeting and exposition, Denver, United States, 13/11/16 - 17/11/16, .

An investigation into drug content uniformity in fused filament fabrication. / Brammer, Elanor; Halbert, Gavin; Lamprou, Dimitrios.

2016. Poster session presented at 2016 AAPS Annual meeting and exposition, Denver, United States.

Research output: Contribution to conferencePoster

TY - CONF

T1 - An investigation into drug content uniformity in fused filament fabrication

AU - Brammer, Elanor

AU - Halbert, Gavin

AU - Lamprou, Dimitrios

PY - 2016/11/17

Y1 - 2016/11/17

N2 - PurposeWith 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.MethodsDrug 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.ResultsAFM 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. ConclusionsThese 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.

AB - PurposeWith 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.MethodsDrug 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.ResultsAFM 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. ConclusionsThese 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.

KW - fused filament fabrication (FFF)

KW - 3D Printing

KW - drug delivery

KW - pharmaceutical manufacturing

UR - http://abstracts.aaps.org/Verify/AAPS2016/PosterSubmissions/33M0400.pdf

UR - https://annual.aapsmeeting.org/

M3 - Poster

ER -

Brammer E, Halbert G, Lamprou D. An investigation into drug content uniformity in fused filament fabrication. 2016. Poster session presented at 2016 AAPS Annual meeting and exposition, Denver, United States.