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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Materials
Micronized dexamethasone (DEX; Euro OTC Pharma GmbH, Bönen, Germany) was used as drug and 17-oxo dexamethasone (OXO; Toronto Chemicals Inc., Toronto, Canada) as reference of its main degradation product. The polymers Eudragit® RS 100 (EuRS; chemically: ammonio methacrylate copolymer; Evonik Industries AG, Essen, Germany), ethyl cellulose (EC; ETHOCEL™ Standard 7 Premium; DuPont, Wilmington, USA) and polyethylene oxide (PEO N10 and PEO 303; POLYOX™ WSR N10 with an approximate molecular weight of 100,000 Da, containing 0.8–3.0% silicon dioxide; and POLYOX™ WSR 303 with an approximate molecular weight of 7,000,000 Da, containing 100–1000 ppm BHT and 0.8–3.0% silicon dioxide; The Dow Chemical Company, Midland, USA) were kindly donated by their suppliers. Triethyl citrate (TEC; Merck KGaA, Darmstadt, Germany), polyethylene glycol 6000 (PEG; Carl Roth GmbH + Co. KG, Karlsruhe, Germany), butylated hydroxytoluene (BHT; Sigma-Aldrich Chemie GmbH, Steinheim, Germany) and tocopherol (Vit E; D-alpha, assay: 89%; Caesar & Loretz GmbH, Hilden, Germany) were used as additives. Further chemicals used were formic acid (Carl Roth GmbH + Co. KG, Karlruhe, Germany or VWR International S.A.S., Rosny-sous-Bois, France), methanol (MeOH) and acetonitrile (ACN; both from VWR International S.A.S., Rosny-sous-Bois, France).
Vanessa Domsta, Tessa Boralewski, Martin Ulbricht, Philipp Schick, Julius Krause, Anne Seidlitz, Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide, International Journal of Pharmaceutics: X, Volume 8, 2024, 100263, ISSN 2590-1567, https://doi.org/10.1016/j.ijpx.2024.100263.
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