Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir

Multicharged cyclodextrin supramolecular assemblies

“…[119][120][121][122][123] Therefore, most reported positively charged functional groups (imidazolium salts, 124 ammonium salts, 125,126 guanidinium salts, 127 etc.) and negatively charged functional groups (carboxylates, [128][129][130][131] phosphates, 132 sulfonates, [133][134][135][136][137][138] etc.) attached to the C-2, C-3, or C-6 hydroxy groups of CDs can interact with oppositely charged molecules through electrostatic interactions.…”

Comparative bioavailability study following a single dose intravenous and buccal administration of remdesivir in rabbits

“…The role of SBECD is to improve both the solubility and stability of remdesivir via inclusion complex formation ( Pipkin et al, 2020 ). Molecular dynamic study proved the interaction between remdesivir and SBECD of various DS ( Garrido et al, 2020 ; Piñeiro et al, 2021 , Piñeiro et al, 2022 ). Recent NMR investigations suggested that the protonation state of the aminopyrrolo-triazine moiety of remdesivir can play a key role in the cyclodextrin-remdesivir interaction ( Várnai et al, 2022 ).…”

“…A follow-up patent application of Jubilant Generics Limited discloses a sublingual or buccal tablet composition of remdesivir using native β -cyclodextrin amongst various excipients, but the corresponding pharmacokinetic data are not provided by the applicant ( Nandi et al, 2021 ). The presence of SBECD in the formulation has the advantage of improved solubility and reduced aggregation of remdesivir ( Piñeiro et al, 2021 ). A recent paper by Szente et al (2021) gave a detailed comparison of the physico-chemical characteristics and dissolution behavior of freeze-dried and electrospun nanofiber forms of SBECD-enabled remdesivir formulation.…”

Supramolecular Biopharmaceutical Carriers Based on Host–Guest Interactions

“…derivatives and remdesivir molecules by molecular dynamics. 51 The formation of small hybrid aggregates between drug molecules was found to act synergistically with the formation of inclusion complexes to favor the bioavailability of the drugs. Feng et al synthesized zwitterionic choline phosphate-functionalized β-cyclodextrin derivatives, which could disrupt the hydrogen network between natural β-CD molecules, and their water solubility was enhanced.…”

“…Other authors simulated the solubilization mechanism between different substituted quantities of sulphobutylether-β-cyclodextrins. derivatives and remdesivir molecules by molecular dynamics . The formation of small hybrid aggregates between drug molecules was found to act synergistically with the formation of inclusion complexes to favor the bioavailability of the drugs.…”