Investigation of the degradation and in-situ amorphization of the enantiomeric drug escitalopram oxalate during Fused Deposition Modeling (FDM) 3D printing
Hot-melt extrusion (HME) and subsequent FDM 3D printing offer great potential opportunities in the formulation development and production of customized oral dosage forms with poorly soluble drugs. However, thermal stress within these processes can be challenging for thermo-sensitive drugs. In this work, three different formulations were prepared to investigate the degradation and the solid state of the thermo-sensitive and poorly soluble drug escitalopram oxalate (ESC-OX) during the two heat-intensive processes HME and FDM 3D printing.
- In-situ amorphization of ESC-OX from bPMMA extrudates during 3D printing.
Degradation of ESC-OX is polymer dependent and lowest with bPMMA.
- No racemization of S-enantiomer was observed during HME and FDM 3D printing.
For this purpose, hydroxypropyl methyl cellulose (HPMC) and basic butylated methacrylate copolymer (bPMMA) were chosen as polymers. DSC and XRD measurements revealed that ESC-OX is amorphous in the HPMC based formulations in both, extrudates and 3D printed tablets. In contrast, in-situ amorphization of the drug from crystalline state in bPMMA filaments was observed during FDM 3D printing. With regard to the content, it was found that degradation of ESC-OX in extrudates with bPMMA could be avoided and in 3D printed tablets almost fully reduced. Furthermore, a possible conversion into the R-enantiomer in the formulation with bPMMA could be excluded using a chiral column. Compared to the commercial product Cipralex®, drug release from extrudates and tablets with bPMMA was slower but still qualified as immediate drug release.
ESC-OX was purchased from F. & A. Pharma-Handels-GmbH (Marl, Germany) ex Micro Labs Limited (Bangalore, India). Hypromellose (HPMC, Affinisol™ HPMC HME 15 LV) and polyethylene oxid Mw 100.000 (PEO, Polyox™ WSR N10) were kindly provided by DuPont Nutrition & Biosciences (Neu-Isenburg, Germany). Basic butylated methacrylate copolymer (bPMMA, Eudragit® E PO) and fumed silica (Aerosil® 200 V/V Pharma) were kindly provided by Evonik (Essen, Germany). Polyethylene glycol (PEG) 6.000 (Polyglykol® 6000 P) was kindly provided by Clariant (Frankfurt, Germany). ESC-OX United States Pharmacopoeia (USP) reference standard, R-Citalopram oxalate USP reference standard, Citalopram Related Compound A USP reference standard (CIT-A), Citalopram Related Compound B USP reference standard (CIT-B) and Citalopram Related Compound C USP reference standard (CIT-C) were purchased by Eurofins PHAST GmbH (Homburg, Germany). Citalopram hydrobromide CRS was purchased at the European Directorate for the Quality of Medicine & Healthcare (Strasbourg, France).
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Lena Hoffmann, Jörg Breitkreutz, Julian Quodbach, Investigation of the degradation and in-situ amorphization of the enantiomeric drug escitalopram oxalate during Fused Deposition Modeling (FDM) 3D printing, European Journal of Pharmaceutical Sciences, Volume 185, 2023, 106423, ISSN 0928-0987,