Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

Abstract

Purpose: To study the interaction between ciprofloxacin hydrochloride (Cipro) and diclofenac sodium (DS) in the presence and absence of metal ions. Methods: Complexes were prepared in the aqueous phase at different molar ratios (r) of Cipro:DS (ranged from 0.2-2.0). The complexes were characterized by Fourier transform-infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and high pressure liquid chromatography (HPLC). Their properties, i.e., solubility, dissolution and partition coefficient (log P), were studied along with their permeability across Caco-2 cells. Furthermore, the antimicrobial activity of Cipro and its complexes was determined using standard broth dilution method and expressed as minimum inhibitory concentration (MIC). Results: Cipro formed an ion pair with DS. The product was confirmed to be a combination of the two drugs, DS and Cipro, but in a ratio that is dependent on the added amounts of each component (r = 1:1 or 1:2). The 1:1 product was more lipophilic than the individual components leading to a lower aqueous solubility and a higher octanol/water partition coefficient log P (6.7 vs. 0.77). The presence of DS within the dissolution medium appeared to modify the dissolution of Cipro depending on the concentration. Moreover, ternary complexes involving Cipro, DS and metal ions (iron and/or calcium) exhibited improved antimicrobial effect (MIC, 0.016 µg/ml compared to 0.258 µg/ml for Cipro). Caco-2 cell permeation data indicate that the presence of DS significantly improved the apparent permeability coefficient (Papp) of Cipro (20.6 × 10-6 cm/s) which was three times higher than that of free Cipro (p < 0.05). DS also appeared to counteract the well-known negative effect of metal ions on the bioavailability of Cipro. Conclusion: There is a clinically relevant interaction between DS and Cipro at the absorption level as a result of ion pair formation, which might even counteract the negative effect of metals on the absorption of Cipro. These findings should aid the design of new Cipro ion pairs that provide higher bioavailability than free Cipro.

Preparation, characterization and antimicrobial assessment of selected ciprofloxacin salts

“…Solubility and apparent partition coefficient studies were performed in triplicate as previously described (8). Briefly, the excess solid material of CP or any of the prepared salts was added to 4 mL of phosphate buffer (pH 6.8), left on a shaker water bath for 24 h and then 1 mL was centrifuged.…”

“…Further investigations IMAD I. HAMDAN 1 DINA EL-SABAWI 2 RULA DARWISH 2 LINA A. DAHABIYEH 1, * from our laboratory, revealed that DS forms ion-pair salts with CP. The resulting salts were shown to have modified physicochemical properties, partition coefficient and, to some extent, antimicrobial activity (8). Ternary associates, involving one molecule of CP and two molecules of DS, have also been shown to form, and, interestingly, possess solubilities different than that of CP or its 1:1 salt.…”

A multibiomarker approach to assess the ecotoxicological effects of diclofenac on Asian clam Corbicula fluminea (O. F. Müller, 1774)

“…The physiological response, alteration of siphon e ciency, has been frequently regarded as an index to evaluate the function of freshwater bivalves in ecology and bioremediation (Hills et al 2020). A previous research has demonstrated that 2.5 µg/L cipro oxacin (CIP), another commonly human pharmaceutical, could signi cantly inhibit the siphon e ciency of Corbicula uminea (El-Sabawi et al 2019;Guo et al 2021). However, whether DCF has the same impact on siphon behavior of bivalves is unclear.…”