Computer-Aided Design of Cefuroxime Axetil/Cyclodextrin System with Enhanced Solubility and Antimicrobial Activity

Abstract

This study aimed to investigate changes in the solubility and antimicrobial efficacy of cefuroxime axetil (CA) when incorporated into cyclodextrin (CD). While choosing the CD, the validated in silico model was used. A theoretical model based on docking and molecular mechanics/generalized born surface area was validated using a curated dataset of API (active pharmaceutical ingredient)–CD stability constants. The library of commonly used cyclodextrins was virtually screened, indicating CA –hydroxypropyl-βCD (HPβCD) as the most thermodynamically favored system. Solid-state CA–HPβCD system was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR), and X-ray diffraction (XRPD) methods. The dissolution profiles of the CA and its cyclodextrin system were evaluated. Microbiological activity of the CA–HPβCD inclusion system was studied based on changes in minimal inhibitory concentration (MIC) values and related to ones of the pure CA. The theoretical model was successfully validated, obtaining an average correlation with experimental data R = 0.7. The dissolution study showed significantly improved dissolution profiles of CA–HPβCD compared to CA. HPβCD increases the antimicrobial efficacy of CA up to 4-fold compared to pure CA.

The Inclusion of Tolfenamic Acid into Cyclodextrins Stimulated by Microenvironmental pH Modification as a Way to Increase the Anti-Migraine Effect

“…The increase in pharmacological activity for API with a different mechanism of action after their introduction into CD cavities, confirmed by the results of in vivo studies were reported, eg, for antimicrobial activity cefuroxime axetil, for the anti-inflammatory activity of naringenin and for reduction of arterial pressure by valsartan. [50][51][52] In our previous studies, we also confirmed that an increase in the analgesic effect for sumatriptan after introduction into CD structures was possible. 23 Other studies confirming the beneficial impact of CD systems on the analgesic effect were also obtained in the case of ketoprofen, where antipyretic, analgesic and anti-inflammatory effects increased, and in the mice study for meloxicam, where the elevated API serum levels maximized its analgesic activity.…”

Hydroxypropyl-β-cyclodextrin as an effective carrier of curcumin – piperine nutraceutical system with improved enzyme inhibition properties

“…Antimicrobial activity for curcumin and piperine in free forms was previously confirmed 59,60 . Also, 2-hydroxypropyl-b-cyclodextrin showed some antibacterial effect 61 , but more importantly, it increases bactericidal effect of other substances 62,63 . Cyclodextrins, according to many mechanisms, can counteract infections by decreasing antibiotic resistance via complexation 64 , lowering the cell-to-cell (quorum sensing) communication 65 , and blocking poreforming toxins 66 .…”

Tedizolid-Cyclodextrin System as Delayed-Release Drug Delivery with Antibacterial Activity

“…For example, meropenem/β-cyclodextrin showed significant changes in MIC values (4.0 mg/mL) against P. aeruginosa compared to meropenem (8.0 mg/mL), what can indicate changes in the permeability of the outer membrane [ 20 ]. Also, significant improvement in water solubility was observed in case of tebipenem pivoxil, where statistically significant increases in dissolution rate were observed in the case of the tebipenem pivoxil/β-cyclodextrin complex [ 21 ], cefuroxime axetil, where after 2 min the cefuroxime axetil/hydroxypropyl-β-cyclodextrin inclusion sample was dissolved in 63%, while pure cefuroxime axetil was only dissolved in 21% [ 22 ], or cetirizine/β-CD for taste-masking purpose [ 23 ]. The use of cyclodextrin-based systems, in addition to affecting the dissolution rate of biomolecules, may also affect the prolonged and/or delayed release of the active from system [ 24 ].…”