Hydrophobic deep eutectic solvent (HDES) as oil phase in lipid-based drug formulations
There is increasing pharmaceutical interest in deep eutectic solvents not only as a green alternative to organic solvents in drug manufacturing, but also as liquid formulation for drug delivery. The present work introduces a hydrophobic deep eutectic solvent (HDES) to the field of lipid-based formulations (LBF). Phase behavior of a mixture with 2:1 M ratio of decanoic- to dodecanoic acid was studied experimentally and described by thermodynamic modelling. Venetoclax was selected as a hydrophobic model drug and studied by atomistic molecular dynamics simulations of the mixtures.
Highlights
- A hydrophobic deep eutectic solvent (HDES) is developed as a novel oil phase for LBFs.
- Phase diagrams are modeled to describe the thermodynamic behavior of the HDES.
- Molecular dynamics simulations are performed to examine the formulation architecture.
- The HDES solubilized more venetoclax compared to conventional oil-phase candidates.
- Combined with Tween 80, the HDES resulted in supersaturated venetoclax release.
As a result, valuable molecular insights were gained into the interaction networks between the different components. Moreover, experimentally the HDES showed greatly enhanced drug solubilization compared to conventional glyceride-based vehicles, but aqueous dispersion behavior was limited. Hence surfactants were studied for their ability to improve aqueous dispersion and addition of Tween 80 resulted in lowest droplet sizes and high in vitro drug release. In conclusion, the combination of HDES with surfactant(s) provides a novel LBF with high pharmaceutical potential. However, the components must be finely balanced to keep the integrity of the solubilizing HDES, while enabling sufficient dispersion and drug release.
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Materials
Venetoclax was purchased from Laurus Labs Ltd. (Telangana, India). The DES components decanoic acid (DeA) and dodecanoic acid (DoA), the surfactants Cremophor EL, DL-α-tocopherol methoxypolyethylene glycol succinate (TPGS) and Poloxamer 188, along with buffer components, HPLC-grade acetonitrile (≥99.9 %), ammonium phosphate monobasic and phosphoric acid solution for pH adjustments, were all purchased from Sigma-Aldrich (Sigma-Aldrich, Steinheim, Germany). Medium chain triglyceride Miglyol® 812 N was kindly provided as a free sample from IOI Oleochemicals (IOI Oleo GmbH, Hamburg, Germany). Gelucire 48/16, Labrasol ALF, Labrafac lipophile WL 1349, and Labrafil M2125 CS were also provided as free samples from Gattefossé (Saint-priest, France), and the Soluplus® was purchased from BASF (BASF SE, Ludwigshafen, Germany). Tween 80 (Ph.Eur. grade) was purchased from Carl Roth GmbH & Co. KG (Karlsruhe, Germany) and food-grade sesame oil was purchased from Momentum Foods Pty Ltd. (Melbourne, Australia).
Shaida Panbachi, Josef Beranek, Martin Kuentz, Hydrophobic deep eutectic solvent (HDES) as oil phase in lipid-based drug formulations, International Journal of Pharmaceutics, 2024, 124418, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124418.
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