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

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.

Grantor dc:publisher.institution

University of Bradford

Author dc:creator

• Achi, Ifunnaya P.K.

Advisors dc:contributor.advisor

• Paluch, Krzysztof J.
• Sheldrake, Helen
• Katsikogianni, Maria

• Antibiotic prodrugs
• Ester prodrugs
• Ciprofloxacin
• Ciprofloxacin esters
• Solubility
• Permeability
• Biopharmaceutical classification system

Statement dc:rights

• <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.

Language dc:language.iso

en

Repository record dc:identifier.uri

https://bradscholars.brad.ac.uk/handle/10454/20594

OAI identifier oai:identifier

oai:bradscholars.brad.ac.uk:10454/20594