Acta Pharm. 64 (2014) 77-88
Original research paper
Biopharmaceutical characterisation of ciprofloxacin-metallic ion
interactions: Comparative study into the effect of aluminium, calcium, zinc and
iron on drug solubility and dissolution
ALEKSANDRA STOJKOVIĆ, LIDIA TAJBER, KRZYSZTOF J.
PALUCH, ZORICA DJURIĆ, JELENA PAROJČIĆ and OWEN I. CORRIGAN
1 Faculty of Pharmacy, University of Belgrade, 11000
Belgrade, Serbia
2 School of Pharmacy and Pharmaceutical Sciences,
Trinity College, University of Dublin, Dublin 2, Ireland
Accepted November 13, 2013
Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)2(Cl)2(ciprofloxacin)2 × nH2O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.
Keywords: ciprofloxacin, dissolution, drug interactions,
solubility, solid state characterisation