Thumbnail Image
Publication

Synthesis, Physicochemical And Biopharmaceutical Characterisation Of Pro-Antibiotic Esters; Free Bases Of Ciprofloxacin

Achi, Ifunnaya P.K.
Citations
Altmetric:
Publication Date
End of Embargo
Supervisor
Paluch, Krzysztof J.
Sheldrake, Helen
Katsikogianni, Maria
Keywords
Antibiotic prodrugs, Ester prodrugs, Ciprofloxacin, Ciprofloxacin esters, Solubility, Permeability, Biopharmaceutical classification system
Rights
Creative Commons License
The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
Open Access status
Accepted for publication
Institution
University of Bradford
Department
School of Pharmacy and Medical Sciences. Faculty of Life Sciences
Awarded
2023
Embargo end date
Collections
Theses
Show all metadata
Files
Thumbnail Image
PhD Thesis
Adobe PDF, 5.73 MB
Additional title
Abstract
Physicochemical and biopharmaceutical properties of drugs play a crucial role in their performance in vivo, especially with respect to oral bioavailability. In the case of antibiotics, poor bioavailability can indirectly encourage antimicrobial resistance from pressure selection resulting from subtherapeutic dosing. This study was designed to synthesise esters of Ciprofloxacin, a model drug using alcohol co-formers (isopentanol, n-butanol and isobutanol) with a view to improving the physicochemical and biopharmaceutical properties of Ciprofloxacin. Three esters of ciprofloxacin were synthesised, i.e., isopentanoate (CIP), n-butanoate (CNB) and isobutanoate (CIB). The effect of esterification on the physicochemical and biopharmaceutical properties of Ciprofloxacin was investigated. Thus, the lipophilicity, solubility, permeability, metabolism and antimicrobial efficacies were studied. The extent of uptake of these esters into E. Coli and S. aureus compared to Ciprofloxacin was also studied. A significant increase in lipophilicity and permeability was noted in all esters, with the branch-chained esters (CIP and CIB) having higher lipophilicity than the straight-chain ester (CNB). Solubility also increased compared to the parent drug, and all esters were successfully bioconverted into the parent compound without loss of activity. Esterification of Ciprofloxacin with isopenatanol, n-butanol and isobutanol improved its physicochemical and biopharmaceutical properties.
URI
https://bradscholars.brad.ac.uk/handle/10454/20594
Version
Citation
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Thesis
Qualification name
PhD
Notes