title: Biopharmaceutical characterization of ciprofloxacin HCl-ferrous sulfate interaction.
abstract: The ciprofloxacin-iron interaction, resulting in a lower bioavailability, is well documented in vivo; however, a mechanistic explanation supported by experimental data of this interaction is missing. In the present study, ciprofloxacin hydrochloride (HCl) and ferrous sulfate interaction was simulated in vitro by performing solubility and dissolution studies in the reactive media containing ferrous sulfate. Characterization of the precipitate formed indicated its probable chemical structure as Fe(SO(4) (2-) )(2) (Cl(-) )(2) (ciprofloxacin)(2) × (H(2) O)(n) , where n is up to 12 molecules of water. The solubility of this complex in water was estimated to be approximately 2  mg/mL, being about 20-fold lower than the solubility of ciprofloxacin HCl. The solubility of the complex was used as input parameter for an in silico modeling by GastroPlus™ and the resulting predicted plasma time curves were in good agreement with the in vivo data. These results strongly indicate that ciprofloxacin-iron interaction in vivo is caused by the formation of a low soluble complex. This interaction was also simulated by in vitro dissolution, in which a mini scale apparatus provided more biorelevant results than the standard dissolution apparatus, probably because the drug concentrations in the mini apparatus were higher and, thus, closer to the conditions encountered in vivo.
authors.affiliation: Faculty of Pharmacy, University of Belgrade, Serbia. jelena.parojcic@pharmacy.bg.ac.rs
authors.forename: Jelena
authors.initials: J
authors.lastname: Parojčić
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stojković
authors.forename: Lidia
authors.initials: L
authors.lastname: Tajber
authors.forename: Sandra
authors.initials: S
authors.lastname: Grbić
authors.forename: Krzysztof J
authors.initials: KJ
authors.lastname: Paluch
authors.forename: Zorica
authors.initials: Z
authors.lastname: Djurić
authors.forename: Owen I
authors.initials: OI
authors.lastname: Corrigan
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D001682:Biological Availability; D002712:Chlorides / Q000032:analysis; D002939:Ciprofloxacin / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D003201:Computers; D004347:Drug Interactions; D005296:Ferrous Compounds / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D012984:Software; D012995:Solubility; D013431:Sulfates / Q000032:analysis
chemical_list: D000890:Anti-Infective Agents; D002712:Chlorides; D005296:Ferrous Compounds; D013431:Sulfates; C020748:ferrous sulfate; D002939:Ciprofloxacin