Solvent electrospinning amorphous solid dispersions with high itraconazole, celecoxib, mebendazole and fenofibrate drug loading and release potential

Jana Becelaere; Olmo Frateur; Ella Schoolaert; Valérie Vanhoorne; Dagmar R D'hooge; Chris Vervaet; Richard Hoogenboom; Karen De Clerck

doi:10.1016/j.jconrel.2023.08.054

Solvent electrospinning amorphous solid dispersions with high itraconazole, celecoxib, mebendazole and fenofibrate drug loading and release potential

J Control Release. 2023 Oct:362:268-277. doi: 10.1016/j.jconrel.2023.08.054. Epub 2023 Sep 1.

Authors

Jana Becelaere¹, Olmo Frateur¹, Ella Schoolaert¹, Valérie Vanhoorne², Dagmar R D'hooge¹, Chris Vervaet³, Richard Hoogenboom⁴, Karen De Clerck⁵

Affiliations

¹ Ghent University, Department of Materials, Textiles and Chemical Engineering, Faculty of Engineering and Architecture, Technologiepark 70A, B-9052 Ghent, Belgium.
² Ghent University, Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
³ Ghent University, Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: chris.vervaet@ugent.be.
⁴ Ghent University, Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Krijgslaan 281 - S4, B-9000 Ghent, Belgium. Electronic address: richard.hoogenboom@ugent.be.
⁵ Ghent University, Department of Materials, Textiles and Chemical Engineering, Faculty of Engineering and Architecture, Technologiepark 70A, B-9052 Ghent, Belgium. Electronic address: karen.declerck@ugent.be.

PMID: 37648083
DOI: 10.1016/j.jconrel.2023.08.054

Abstract

In this work, the feasibility of ultra-high drug loaded amorphous solid dispersions (ASDs) for the poorly soluble itraconazole, mebendazole and celecoxib via solvent electrospinning in combination with poly(2-ethyl-2-oxazoline) and fenofibrate in combination with polyvinylpyrrolidone is demonstrated. By lowering the polymer concentration in the electrospinning solution below its individual spinnable limit, ASDs with a drug content of up to 80 wt% are obtained. This is attributed to drug-polymer interactions not being limited by default to hydrogen bonds, as also Van der Waals interactions can result in high drug loadings. The theoretically predicted miscibility by the Flory-Huggins theory is corroborated by the experimental findings based on (modulated) differential scanning calorimetry and x-ray diffraction. Globally, the maximally obtained amorphous drug loadings are higher compared to the loadings found in literature. Additionally, non-sink dissolution tests demonstrate an increase in solubility of up to 50 times compared to their crystalline counterparts. Moreover, due to the lack of precipitation biocompatible PEtOx succeeds in stabilizing the dissolved drug and inhibiting its instant precipitation. The current work thus demonstrates the broader applicability of the electrospinning technique for the production of physically stable ASDs with ultra-high drug loadings, a result which has been validated for several Biopharmaceutics Classification System class II drugs.

Keywords: Amorphous solid dispersions (ASDs); Flory-Huggins; Poly(2-ethyl-2-oxazoline) (PEtOx); Poorly soluble drugs; Solubility enhancement; Solvent electrospinning.