Molecular Structure of Cefuroxime Axetil Complexes with α-, β-, γ-, and 2-Hydroxypropyl-β-Cyclodextrins: Molecular Simulations and Raman Spectroscopic and Imaging Studies

Abstract

The formation of cefuroxime axetil+cyclodextrin (CA+CD) complexes increases the aqueous solubility of CA, improves its physico-chemical properties, and facilitates a biomembrane-mediated drug delivery process. In CD-based tablet formulations, it is crucial to investigate the molecular details of complexes in final pharmaceutical preparation. In this study, Raman spectroscopy and mapping were applied for the detection and identification of chemical groups involved in α-, β-, γ-, and 2-hydroxypropyl-β-CD (2-HP- β-CD)+CA complexation process. The experimental studies have been complemented by molecular dynamics-based investigations, providing additional molecular details of CA+CD interactions. It has been demonstrated that CA forms the guest–host type inclusion complexes with all studied CDs; however, the nature of the interactions is slightly different. It seems that both α- and β-CD interact with furanyl and methoxy moieties of CA, γ-CD forms a more diverse pattern of interactions with CA, which are not observed in other CDs, whereas 2HP-β-CD binds CA with the contribution of hydrogen bonding. Apart from supporting this interpretation of the experimental data, molecular dynamics simulations allowed for ordering the CA+CD binding affinities. The obtained results proved that the molecular details of the host–guest complexation can be successfully predicted from the combination of Raman spectroscopy and molecular modeling.

Adsorption of Paraquat by Poly(Vinyl Alcohol)-Cyclodextrin Nanosponges

“…The pristine β-CD spectra exhibited the characteristic bands at 1463 cm −1 for CH deformation, 1414 cm −1 for C–O–C symmetric and antisymmetric stretching, 1389 cm −1 for CH stretching and wagging, 1338 cm −1 for CH 2 deformation, 1252 cm −1 for OH in plane bending and CH 2 stretching, 1125 cm −1 for C–O–C symmetric stretching, 1081 cm −1 for C–O–C symmetric and antisymmetric stretching of glycosidic bonds, 1041 cm −1 for C–O stretching, 947 cm −1 for skeletal mode of α-(1–4) linkage (delocalized mode), 931 cm −1 for glucopyranose (C–O–C) skeletal mode of α-anomers, 855 cm −1 for OCH side group deformational of d -glucopyranose units, 757 cm −1 for d -glucopyranose ring breathing mode, 709 cm −1 for CH out of plane bending, 575 cm −1 for OH wagging, 479 cm −1 for skeletal vibrations of amylose, 439 cm −1 for CH stretching, 356 cm −1 for OH stretching, 318 cm −1 for external C–OH out of plane bending of glucopyranose units, and 155 cm −1 for the breathing motions of oxygen atoms in the macrocyclic ring. These results were in agreement with the literature [ 89 , 90 , 91 , 92 ].…”

Adsorption of Cationic Contaminants by Cyclodextrin Nanosponges Cross-Linked with 1,2,3,4-Butanetetracarboxylic Acid and Poly(vinyl alcohol)

“…The β-CD spectra exhibited the specific bands at 1463 cm −1 for CH deformation, 1338 cm −1 for CH 2 deformation, 1252 cm −1 for OH in-plane bending and CH 2 stretching, 1125 cm −1 for C-O-C symmetric stretching, 1081 cm −1 for C-O-C symmetric and antisymmetric stretching of glycosidic bonds, and 479 cm −1 for skeletal vibrations of amylose. These results were in agreement with the literature [133][134][135][136]. For BP5 nanosponges, the particular peaks were found at 1229 cm −1 for CH 2 stretching, 1144 cm −1 for CC and CO stretching, 1043 cm −1 for C-O stretching, and 810 cm −1 for C-O-C stretching.…”

Cyclodextrin Inclusion Complexes with Antibiotics and Antibacterial Agents as Drug-Delivery Systems—A Pharmaceutical Perspective

“…Another study showed the affinity order of four CDs for cefuroxime axetils as follows: HP-β-CD ~ γ-CD > β-CD ~ α-CD [ 69 ]. Raman spectroscopy and mapping, along with a molecular dynamics simulation, showed that α- and β-CD interact with the furanyl and methoxy moieties of cefuroxime axetil, and γ-CD creates a more diverse interaction pattern with the parent drug, while HP-β-CD binds cefuroxime axetil with the contribution of hydrogen bonding.…”