TY - THES

T1 - Effect of weld lines on in-vitro drug release from additively manufactured pharmaceutical devices of ethylene vinyl acetate (EVA) produced via material extrusion (MEX)

AU - Gomez Contreras, Andrea

N1 - embargoed until 06-11-2028

PY - 2023

Y1 - 2023

N2 - Ethylene vinyl acetate (EVA) with 28 wt.% VA (EVA28) is an important carrier polymer for controlled release drug delivery. Its processability via additive manufacturing (AM) has been recently demonstrated. The EVA28 properties have led this copolymer to multiple commercial drug delivery systems (DDS), via traditional manufacturing processes, such as hot melt extrusion or injection molding following the ¿one size fits all¿ approach. This DDS generally are accompanied by different active pharmaceutical ingredients (APIs) such as progesterone (P4), with the characteristic of being used for long term therapy treatments. These treatments usually require a controlled drug release to be effective. To pursue another fabrication method that allows personalized drug release and size for each patient needs, the AM production of this devices has been researched. For this reason, the aim of this work was to search 3D-printing parameters for AM that influence the formation of weld lines appearance and systematically examine their impact based on the orientation of these weld lines on the in-vitro release of P4 from a device using EVA28/P4 as its base material. To do so, the highest and the lowest process parameters for nozzle temperature and print speed were identified, combined with two different printing modes (single vs triplicate) and tested via in-vitro dissolution. They were quantified via ultra-high performance liquid chromatography (UPLC), and the data was fitted using the Higuchi and Korsmeyer-peppas equations. The various analyzed parameters significantly impacted the direction-dependent in-vitro drug release of P4. The study revealed that the parameters governing weld line formation exert influence on drug release. This influence extends beyond the physical aspect, not only impeding diffusion in the perpendicular direction, but also affects the state of P4 on the EVA28 matrix, leading to the creation of supersaturated solutions within EVA28 upon thermal treatment.

AB - Ethylene vinyl acetate (EVA) with 28 wt.% VA (EVA28) is an important carrier polymer for controlled release drug delivery. Its processability via additive manufacturing (AM) has been recently demonstrated. The EVA28 properties have led this copolymer to multiple commercial drug delivery systems (DDS), via traditional manufacturing processes, such as hot melt extrusion or injection molding following the ¿one size fits all¿ approach. This DDS generally are accompanied by different active pharmaceutical ingredients (APIs) such as progesterone (P4), with the characteristic of being used for long term therapy treatments. These treatments usually require a controlled drug release to be effective. To pursue another fabrication method that allows personalized drug release and size for each patient needs, the AM production of this devices has been researched. For this reason, the aim of this work was to search 3D-printing parameters for AM that influence the formation of weld lines appearance and systematically examine their impact based on the orientation of these weld lines on the in-vitro release of P4 from a device using EVA28/P4 as its base material. To do so, the highest and the lowest process parameters for nozzle temperature and print speed were identified, combined with two different printing modes (single vs triplicate) and tested via in-vitro dissolution. They were quantified via ultra-high performance liquid chromatography (UPLC), and the data was fitted using the Higuchi and Korsmeyer-peppas equations. The various analyzed parameters significantly impacted the direction-dependent in-vitro drug release of P4. The study revealed that the parameters governing weld line formation exert influence on drug release. This influence extends beyond the physical aspect, not only impeding diffusion in the perpendicular direction, but also affects the state of P4 on the EVA28 matrix, leading to the creation of supersaturated solutions within EVA28 upon thermal treatment.

KW - Drug release

KW - Higuchi model

KW - Additive manufacturing

KW - Wirkstofffreisetzung

KW - Higuchi-Modell

KW - Additive Fertigung

U2 - 10.34901/mul.pub.2024.028

DO - 10.34901/mul.pub.2024.028

M3 - Master's Thesis

ER -