A Supramolecular Assembly Formed by Heteroassociation of Ciprofloxacin and Norfloxacin in the Solid State: Co-Crystal Synthesis and Characterization

Abstract

The interaction in the solid state between ciprofloxacin (CIP) and norfloxacin (NOR) was investigated and a new multicomponent molecular complex (COP) was obtained and characterized. It is composed of equimolar quantities of both compounds, according to TLC and 1 H NMR data. As single-crystal X-ray analysis showed, COP crystallizes in the triclinic system, space group P(1̅ ). The asymmetric unit comprises three independent zwitterions (A, B, and C) with contributions of both CIP and NOR, as well as 14.6 water molecules. At the zwitterion A site, the occurrence is about 37% (CIP), 63% (NOR); at the B site, there is predominantly CIP (70%); and at the C site the occurrence is about 43% (CIP) and 57% (NOR), yielding an overall 1:1 CIP-NOR ratio in the crystal. TG data evidenced a one-step loss of solvent (about 18% per COP zwitterion) below 110 °C, confirming the presence of water molecules. The propensity for heteroassociation between CIP and NOR, under the conditions described herein, originated a co-crystal reported for the first time between FQs, and became one of the most interesting aspects of this research.

Pharmaceutical salts of ciprofloxacin with dicarboxylic acids

“…In addition, the so-called drug-drug salt forms of CIP with non-steroidal anti-inflammatory drugs, diflunisal and indoprofen, have recently been obtained and characterized (Bag et al, 2014). While, Vitorino et al (2013) were able to isolate a multicomponent molecular complex comprising ciprofloxacin and norfloxacin ions in the solid state. It has recently been reported that new ciprofloxacin salts enhance the aqueous solubility and simultaneously influence the octanol-water partition coefficient of the drug, which allows the tuning of relevant pharmacological properties by the counter ion alteration (Florindo et al, 2014).…”

Supramolecular complex of norfloxacin and sulfamethoxazole: Synthesis, characterization, and evaluation of the antibacterial activity

“…The obtained solid was analyzed by melting point (m.p), 1 H MNR, Hot Stage Microscopy, Differential Scanning Calorimetry (DSC), Thermogravimetry, Powder X-ray Diffraction (PXRD) and DRIFT. 1 The antibacterial effect of NOR, SMX and NOR-SMX was evaluated against Escherichia coli ATCC 25922 using the macrodilution method and checkerboard. The minimum inhibitory concentration (MIC) and the fractional inhibitory concentration (CIF) were determined.…”

Cooperative Behavior of Fluoroquinolone Combinations against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>

“…19) In this co-crystal phase there are three independent drug molecule sites which accommodate different proportions of CIP and NOR such that the overall stoichiometry is 1 : 1. In addition to the presence of strong charge-assisted N + -H ...…”

“…those of COP and a triclinic modification of CIP). [19][20][21] Figure 1 highlights the above molecular interactions as they occur in the COP co-crystal phase.…”