Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide.

Hot-melt extrusion (HME) potentially coupled with 3D printing is a promising technique for the manufacturing of dosage forms such as drug-eluting implants which might even be individually adapted to patient-specific anatomy. However, these manufacturing methods involve the risk of thermal degradation of incorporated drugs during processing. In this work, the stability of the anti-inflammatory drug dexamethasone (DEX) was studied during HME using the polymers Eudragit® RS, ethyl cellulose and polyethylene oxide. The extrusion process was performed at different temperatures. Furthermore, the influence of accelerated screw speed, the addition of the plasticizers triethyl citrate and polyethylene glycol 6000 or the addition of the antioxidants butylated hydroxytoluene and tocopherol in two concentrations were studied. The DEX recovery was analyzed by a high performance liquid chromatography method suitable for the detection of thermal degradation products. The strongest impact on the drug stability was found for the processing temperature, which was found to reduce the DEX recovery to <20% for certain processing conditions. In addition, differences between tested polymers were observed, whereas the use of additives did not result in remarkable changes in drug stability. In conclusion, suitable extrusion parameters were identified for the processing of DEX with high drug recovery rates for the tested polymers. Moreover, the importance of a suitable analysis method for drug stability during HME that is influenced by several parameters was highlighted.

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© 2024 The Authors. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vanessa Domsta, Martin Ulbricht, Philipp Schick reports financial support was provided by Federal Ministry of Education and Research of Germany. Vanessa Domsta on behalf of all authors reports equipment, drugs, or supplies was provided by Evonik Industries AG, Essen, Germany. Vanessa Domsta on behalf of all authors reports equipment, drugs, or supplies was provided by DuPont, Wilmington, USA. Vanessa Domsta on behalf of all authors reports equipment, drugs, or supplies was provided by The Dow Chemical Company, Midland, USA. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Authors declared no conflict of interest. As previously stated, this work was financially supported by the 10.13039/501100002347Federal Ministry of Education and Research of Germany (BMBF), “RESPONSE–Partnership for Innovation in Implant Technology” in the program “Zwanzig20– Partnership for Innovation”. The authors thank Thomas Brand for his technical assistance and the suppliers of the used polymers for providing Eudragit®, ETHOCEL™ and POLYOX™ samples.