Ciprofloxacin salts with benzoic acid derivatives: structural aspects, solid-state properties and solubility performance

Surov, Artem O.; Vasilev, Nikita A.; Voronin, Alexander P.; Churakov, Andrei V.; Emmerling, Franziska; Perlovich, German L.

doi:10.1039/d0ce00514b

Cited by 17 publications

(19 citation statements)

References 54 publications

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“…In most of the papers cited above, short (strong) intermolecular H-bonds [22] are not considered since they are practically not realized in single-component crystals. On the other hand, such H-bonds determine the structure of multicomponent molecular crystals used in pharmaceuticals [23][24][25] and crystal engineering [26]. Intermolecular H-bonds of different types and strengths play a decisive role in the structure of crystal hydrates [27,28] and peroxosolvates [29,30].…”

Section: Introductionmentioning

confidence: 99%

Fast Quantum Approach for Evaluating the Energy of Non-Covalent Interactions in Molecular Crystals: The Case Study of Intermolecular H-Bonds in Crystalline Peroxosolvates

et al. 2022

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Energy/enthalpy of intermolecular hydrogen bonds (H-bonds) in crystals have been calculated in many papers. Most of the theoretical works used non-periodic models. Their applicability for describing intermolecular H-bonds in solids is not obvious since the crystal environment can strongly change H-bond geometry and energy in comparison with non-periodic models. Periodic DFT computations provide a reasonable description of a number of relevant properties of molecular crystals. However, these methods are quite cumbersome and time-consuming compared to non-periodic calculations. Here, we present a fast quantum approach for estimating the energy/enthalpy of intermolecular H-bonds in crystals. It has been tested on a family of crystalline peroxosolvates in which the H∙∙∙O bond set fills evenly (i.e., without significant gaps) the range of H∙∙∙O distances from ~1.5 to ~2.1 Å typical for strong, moderate, and weak H-bonds. Four of these two-component crystals (peroxosolvates of macrocyclic ethers and creatine) were obtained and structurally characterized for the first time. A critical comparison of the approaches for estimating the energy of intermolecular H-bonds in organic crystals is carried out, and various sources of errors are clarified.

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Section: Introductionmentioning

confidence: 99%

Fast Quantum Approach for Evaluating the Energy of Non-Covalent Interactions in Molecular Crystals: The Case Study of Intermolecular H-Bonds in Crystalline Peroxosolvates

et al. 2022

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“…Figure 9 a shows that LF-35 was also a salt form. Both DHBA isomers used were in anion form with COO– having almost similar C–O bond lengths (1.267 to 1.269 Å) due to resonance stabilization in the carboxylate anion [ 52 , 53 ]. Because the multicomponent systems were salts, hereafter, LF-26 can be referred to as levofloxacin 2,6 dihydroxybenzoate, while LF-35 represents levofloxacin 3,5 dihydroxybenzoate.…”

Section: Resultsmentioning

confidence: 99%

Stability and Antibiotic Potency Improvement of Levofloxacin by Producing New Salts with 2,6- and 3,5-Dihydroxybenzoic Acid and Their Comprehensive Structural Study

et al. 2022

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Recently, solid-state engineering has become a promising approach to improving the stability and potency of antibiotics. Levofloxacin (LF) is a broad-spectrum fluoroquinolone antibiotic marketed in solid and solution dosage forms. However, this substance forms solid hydrates under ambient conditions and degrades due to lighting, which may change its solid properties and dose. In addition, resistance cases have been reported due to long-time antibiotic usage. This research aims to allow LF to react with antioxidant dihydroxybenzoic acid (DHBA), which has low antimicrobial activity, to produce a more stable compound under water and lighting conditions and improve LF’s potency. The experiment begins with a screening to select potential DHBA isomers that can react with LF and predict the stoichiometric ratio using phase diagrams, which show that 2,6-DHBA and 3,5-DHBA are prospective antioxidants that can react with LF in a (1:1) molar ratio. Multicomponent systems are prepared by dissolving the LF–DHBA mixture in (1:1) ethanol–methanol (95% grade) and evaporating it. Then, the new solid phase formation is confirmed by thermal analysis and powder X-ray diffractometry. Next, infrared spectrophotometry and neutron magnetic resonance analyses are used to identify the LF–DHBA’s interactions. Finally, single-crystal X-ray diffractometry is used to solve the three-dimensional structure of the multicomponent system. We then conduct a hygroscopicity and stability test followed by a lighting and potency test using the microdilution method. Our data reveal that both reactions produce salts, which are named LF-26 and LF-35, respectively. Structurally, LF-26 is found in an anhydrous form with a triclinic crystal packing, while LF-35 is a hemihydrate in a monoclinic system. Afterward, both salts are proven more stable regarding water adsorption and UV lighting than LF. Finally, both multicomponent systems have an approximately two-fold higher antibiotic potency than LF. LF-26 and LF-35 are suitable for further development in solid and liquid dosage formulations, especially LF-35, which has superior stability compared with LF-26.

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“…Several crystal structures of ciprofloxacin salts with benzoic acid derivatives have been reported, including salts with salicylic acid (Surov et al, 2019;Nagalapalli & Yaga Bheem, 2014; CSD refcode family DOFWUT), 4-hydroxybenzoic acid (Surov et al, 2020; CSD refcode PUNMUJ), 4-aminobenzoic acid (Surov et al, 2020; CSD refcode PUNMIX) and gallic acid (Surov et al, 2020;CSD refcode PUNMOD). A search for salt co-crystals of ciprofloxacin hydrochloride yielded one reported crystal structure, a co-crystal of ciprofloxacin hydrochloride with 4-hydroxybenzoic acid (Martı ´nez-Alejo et al, 2014; CSD refcode XOHTUL).…”

Section: Database Surveymentioning

confidence: 99%

Ciprofloxacin salt and salt co-crystal with dihydroxybenzoic acids

Nugraha¹,

Sugiyama²,

Uekusa³

2022

Acta Cryst E

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The crystal structure of two multi-component crystals of ciprofloxacin [systematic name: 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)quinoline-3-carboxylic acid], a fluoroquinolone antibiotic, namely, ciprofloxacin 2,6-dihydroxybenzoate salt, C17H19FN3O3 +·C7H5O4 −, (I), and ciprofloxacin hydrochloride–3,5-dihydroxybenzoic–water (1/1/1), C17H19FN3O3 +·Cl−·C7H6O4·H2O, (II), were determined. In (I) and (II), the ciprofloxacin cations are connected via head-to-tail N—H...O hydrogen bonding. Both structures show an alternating layered arrangement between ciprofloxacin and dihydroxybenzoic acid.

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Ciprofloxacin salts with benzoic acid derivatives: structural aspects, solid-state properties and solubility performance

Abstract: In this work, three new pharmaceutical hydrated salts of ciprofloxacin with selected derivatives of benzoic acid were obtained and systematically investigated by several solid-state analytical techniques.

Cited by 17 publications

References 54 publications

Fast Quantum Approach for Evaluating the Energy of Non-Covalent Interactions in Molecular Crystals: The Case Study of Intermolecular H-Bonds in Crystalline Peroxosolvates

Fast Quantum Approach for Evaluating the Energy of Non-Covalent Interactions in Molecular Crystals: The Case Study of Intermolecular H-Bonds in Crystalline Peroxosolvates

Stability and Antibiotic Potency Improvement of Levofloxacin by Producing New Salts with 2,6- and 3,5-Dihydroxybenzoic Acid and Their Comprehensive Structural Study

Ciprofloxacin salt and salt co-crystal with dihydroxybenzoic acids

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