@inproceedings{01HHKSJAXKY6K53AREEXFV198F,
  abstract     = {{Unfortunately, approximately 40% of all marketed drugs and over 90% of medicines in development suffer from poor aqueous solubility and hence limited bioavailability upon oral administration. This critical, current challenge in pharmaceutics has led to an increased interest in advanced aqueous solubility-enhancing strategies, with the formulation of amorphous solid dispersions (ASDs) as one of the most promising routes. Here, the active pharmaceutical ingredient is ideally molecularly dispersed in a polymeric carrier, hence increasing its chemical potential with respect to its highly stable crystalline counterpart and improving the thermodynamic driving force for dissolution in the gastrointestinal fluids. Nonetheless, the amount of marketed ASDs is still limited, as many ASDs lack physical stability due to their amorphous nature, and recrystallization to their less soluble state during production, downstream processing, storage, and dissolution often limits the applicability. In this research, an important step is taken towards the bioavailability improvement of poorly water-soluble drugs through the formulation of stable ASDs, with flubendazole (FBZ), itraconazole (ITC), mebendazole (MBZ), and celecoxib (CCX) as known Biopharmaceutics Classification System (BCS) class II model compounds. Solvent electrospinning of a working solution of the drug and poly(2-ethyl-2-oxazoline) is put forward, because of the extremely fast solvent evaporation, which freezes the API in the polymeric carrier in a highly homogeneous manner. This work demonstrates the viability and broad applicability of this strategy to produce stable nanofibrous ASDs with ultrahigh drug loadings (up to 55, 60, 70, and 80 wt% for FBZ, ITC, MBZ, and CCX, respectively) and long-term stability (at least one year). Importantly, at such high drug loadings, lowering the concentration of the polymer in the electrospinning solution below the concentration where it can be spun in the absence of the drug is essential, as the interactions between the polymer and the drug result in an increased solution viscosity. A combination of experimental analysis and molecular dynamics simulations revealed that this formulation strategy provides strong, dominant, and highly stable hydrogen bonds between the polymer and the drug, which is crucial to obtain the high drug loadings and to preserve the long-term amorphous character of the ASDs upon storage. In vitro drug release studies confirm the remarkable potential of this electrospinning formulation strategy by significantly increasing drug solubility values (e.g. up to 50 times for ITC after 5 hours) and dissolution rates, even after one-year storage of the formulations (as tested for FBZ).}},
  articleno    = {{SB09.08.09}},
  author       = {{Frateur, Olmo and Becelaere, Jana and Vervaet, Chris and Hoogenboom, Richard and De Clerck, Karen}},
  booktitle    = {{2023 MRS Fall Meeting & Exhibit, Abstracts}},
  language     = {{eng}},
  location     = {{Boston, Massachusetts, USA + Virtual}},
  pages        = {{SB09.08.09:1000--SB09.08.09:1001}},
  publisher    = {{Materials Research Society (MRS)}},
  title        = {{Increasing aqueous drug solubility by solvent electrospinning of poly(2-ethyl-2-oxazoline) based stable amorphous solid dispersions with high drug loading}},
  url          = {{https://www.mrs.org/meetings-events/fall-meetings-exhibits/2023-mrs-fall-meeting/symposium-sessions#program}},
  year         = {{2023}},
}