Cyclodextrin-based supramolecular deep eutectic solvent (CycloDES): A vehicle for the delivery of poorly soluble drugs

Int J Pharm. 2023 Nov 25:647:123553. doi: 10.1016/j.ijpharm.2023.123553. Epub 2023 Oct 24.

Abstract

The aim of this work was to develop a new class of deep eutectic solvent (DES) composed of a complexation agent, namely hydroxy-propyl-β-cyclodextrin (HPβCD), to exploit a synergic solubilization-enhancing approach. For this purpose, cyclodextrin-based supramolecular DES (CycloDES) were physical-chemical characterized and loaded with three different BCS class II model drugs, specifically Cannabidiol, Indomethacin, and Dexamethasone, evaluating the influence of different factors on the observed solubility and permeation compared with the only HPβCD/drug complexation. Hence, CycloDESs were presented as a possible vehicle for drugs and represent a novel potential approach for solving BCS class II and IV solubility issues, demonstrating at least a 100-fold improvement in the investigated drug solubilities. Furthermore, CycloDESs demonstrated a significantly improved resistance to dilution preserving a high percentage of drug in solution (i.e. 93% for Indomethacin) when water is added to the DES if compared with a glucose-choline chloride DES, used as a standard. This evidence guarantees the solubility-enhancing effect useful for the delivery of BCS class II and IV drugs converting solid raw material to advantageous liquid vehicles bypassing the rate-determining dissolution step.

Keywords: BCS class II; Choline Chloride; Cyclodextrins; DES; Drug delivery; Solubility.

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Cyclodextrins* / chemistry
  • Deep Eutectic Solvents
  • Indomethacin
  • Pharmaceutical Preparations / chemistry
  • Solubility

Substances

  • Pharmaceutical Preparations
  • Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Deep Eutectic Solvents
  • Indomethacin