Solubility behavior and biopharmaceutical classification of novel high-solubility ciprofloxacin and norfloxacin pharmaceutical derivatives.
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.
Breda
Susana A
SA
CONICET-Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria (5000), Córdoba, Argentina.
Jimenez-Kairuz
Alvaro F
AF
Manzo
Ruben H
RH
Olivera
María E
ME
D001702:Biopharmaceutics; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000145:classification; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D009643:Norfloxacin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000145:classification; D010539:Permeability; D012995:Solubility; D013607:Tablets
D005079:Excipients; D013607:Tablets; D002939:Ciprofloxacin; D009643:Norfloxacin