3D-printed EVA-based patches manufactured by direct powder extrusion for personalized transdermal therapies

This document is the Submitted Manuscript version of a Published article 1 that appeared in final form in see
International Journal of Pharmaceutics, copyright ELSEVIER.
To access the final edited and published work see: https://doi.org/10.1016/j.ijpharm.2023.122720

3D-printed EVA-based patches manufactured by direct powder extrusion for personalized transdermal therapies
Giorgia Maurizii1, Sofia Moroni1, Shiva Khorshid1, Annalisa Aluigi1, Mattia Tiboni1*, and Luca
1Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento, 6, 61029 Urbino
(PU), Italy.
2 Prosopika srl, Via del Trabocchetto, 1, 61034, Fossombrone (PU), Italy.

Sofia Moroni acknowledge Marche Region for the PhD scholarship (Innovative doctoral programme POR
Marche FSE 2014/2020 D.R. 354/2020).
This research received funding from Regione Marche (Italy) POR MARCHE FESR 2014–2020 – Asse 1 – OS
Azione 2.1 
Si ringrazia la Regione Marche per aver finanziato la borsa di Sofia Moroni attraverso i Dottorati Innovativi.

In recent years, 3D printing has attracted great interest in the pharmaceutical field as a promising tool for the
on-demand manufacturing of patient-centered pharmaceutical forms. Among the existing 3D printing
techniques, direct powder extrusion (DPE) has been demonstrated as the most practical approach thanks to its
high flexibility, low cost, and simplicity. The main goal of this work was to determine whether different grades
of ethylene vinyl acetate (EVA) copolymer might be employed as new feedstock materials for the DPE
technique to manufacture transdermal patches. By selecting two model drugs with different thermal behavior,
we also wanted to pay attention to the versatility of EVA excipient in preparing patches for customized
transdermal therapies. EVA polymeric matrices were loaded with 30% (w/w) of the model drug. Both
formulations were successfully processed with the DPE technique. The physicochemical composition of the
printed devices was investigated through Fourier-transform infrared spectroscopy, differential scanning
calorimetry, and thermogravimetric analyses. Lastly, the drug release and permeation profile of the printed
systems was evaluated for 48 hours and showed to be dependent on the VA content of the EVA grade. Hence,
this study demonstrated that EVA and direct powder extrusion technique could be promising tools for
manufacturing transdermal patches. By selecting the EVA grade with the appropriate VA content, drugs with
dissimilar melting points could be printed preserving their thermal stability. Moreover, the desired drug release
and permeation profile of the drug can be achieved, representing an important advantage in terms of
personalized medicine.

Keywords: Direct Powder Extrusion (DPE); Ethyl vinyl acetate (EVA) copolymer; Transdermal patches;
Personalized medicine; Additive manufacturing

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