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1762853 
Journal Article 
Solubility behavior and biopharmaceutical classification of novel high-solubility ciprofloxacin and norfloxacin pharmaceutical derivatives 
Breda, SA; Jimenez-Kairuz, AF; Manzo, RH; Olivera, ME 
2009 
Yes 
International Journal of Pharmaceutics
ISSN: 0378-5173
EISSN: 1873-3476 
371 
1-2 
106-113 
19150493 
WOS:000265361300014 
The hydrochlorides of the 1:3 aluminum: norfloxacin and
aluminum:ciprofloxacin complexes were characterized according to the Biopharmaceutics
Classification System (BCS) premises in comparison with their parent compounds. The pH-solubility
profiles of the complexes were experimentally determined at 25 and 37 degrees C in the range of
pH 1-8 and compared to that of uncomplexed norfloxacin and ciprofloxacin. Both complexes are
clearly more soluble than the antibiotics themselves, even at the lowest solubility pHs. The
increase in solubility was ascribed to the species controlling solubility, which were analyzed in
the solid phases at equilibrium at selected pHs. Additionally, permeability was set as low, based
on data reported in the scientific literature regarding oral bioavailability, intestinal and cell
cultures permeabilities and also considering the influence of stoichiometric amounts of aluminum.
The complexes fulfill the BCS criterion to be classified as class 3 compounds (high
solubility/low permeability). Instead, the active pharmaceutical ingredients (APIs) currently
used in solid dosage forms, norfloxacin and ciprofloxacin hydrochloride, proved to be BCS class 4
(low solubility/low permeability). The solubility improvement turns the complexes as potential
biowaiver candidates from the scientific point of view and may be a good way for developing more
dose-efficient formulations. An immediate release tablet showing very rapid dissolution was
obtained. Its dissolution profile was compared to that of the commercial ciprofloxacin
hydrochloride tablets allowing to dissolution of the complete dose at a critical pH such as 6.8.
(C) 2008 Elsevier B.V. All rights reserved. 
Biopharmaceutics Classification System (BCS); Dissolution rate; Solubility; Formulation; Permeability; Tableting; Complexation