Packing Interactions in Hydrated and Anhydrous Forms of the Antibiotic Ciprofloxacin: a Solid-State NMR, X-ray Diffraction, and Computer Simulation Study

Mafra, Luís; Santos, Sérgio M.; Siegel, Renée; Alves, Inês; Paz, Filipe A. Almeida; Dudenko, Dmytro; Spiess, Hans Wolfgang

doi:10.1021/ja208647n

Cited by 126 publications

(137 citation statements)

References 16 publications

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“…Solid-state NMR is a unique method that offers access to molecular packing details for polymers and other organic-based materials [29][30][31][32][33] and to details about the donor-acceptor packing in CDT-BTZ polymers [34,35]. For CDT-BTZ-C16, we were able to show from a combination of X-ray diffraction and solid-state NMR that the CDT-BTZ polymer chains self-assemble into π-stacks, where the single polymer chain includes alternating CDT units, pointing in opposite directions (packing in a staggered fashion) and BTZ moieties stacked in an antiparallel configuration along the π-stacking direction [13].…”

Section: Resultsmentioning

confidence: 99%

Solid-State Organization and Ambipolar Field-Effect Transistors of Benzothiadiazole-Cyclopentadithiophene Copolymer with Long Branched Alkyl Side Chains

et al. 2013

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Abstract:The solid-state organization of a benzothiadiazole-cyclopentadithiophene copolymer with long, branched decyl-tetradecyl side chains (CDT-BTZ-C14,10) is investigated. The C14,10 substituents are sterically demanding and increase the π-stacking distance to 0.40 nm from 0.37 nm for the same polymer with linear hexadecyls (C16). Despite the bulkiness, the C14,10 side chains tend to crystallize, leading to a small chain-to-chain distance between lamellae stacks and to a crystal-like microstructure in the thin film. Interestingly, field-effect transistors based on solution processed layers of CDT-BTZ-C14,10 show ambipolar behavior in contrast to CDT-BTZ-C16 with linear side chains, for which hole transport was previously observed. Due to the increased π-stacking distance, the mobilities are only 6 × 10

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Section: Resultsmentioning

confidence: 99%

Solid-State Organization and Ambipolar Field-Effect Transistors of Benzothiadiazole-Cyclopentadithiophene Copolymer with Long Branched Alkyl Side Chains

et al. 2013

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“…Intermolecular C-H π−π interactions between the aromatic rings and between the aromatic ring and cyclopropyl group are also present. 38 kJ/mol, respectively, and therefore the zwitterionic form of CIP (crystal) is more stable. This is consistent with the theoretical density of 1.50 g/cm 3 for CIP_ZW, in comparison to 1.45 g/cm 3 for CIP_UI (calculations performed by Platon software).…”

Section: Crystal Forms Of Ciprofloxacinmentioning

confidence: 99%

Two Faces of Ciprofloxacin: Investigation of Proton Transfer in Solid State Transformations

Mesallati

Mugheirbi

Tajber

2016

Crystal Growth & Design

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Ciprofloxacin (CIP) can exist in two different forms: the zwitterion and the unionized form. While the crystal structure of each has been described independently, the ability of CIP to transform from one to the other in the solid state has not been described. The crystal structures of unionized and zwitterionic CIP were therefore compared using computational methods, including their packing arrangement, hydrogen bonding, packing energy, intermolecular potentials and HOMO/LUMO energy gap. The pure amorphous form of CIP has also never been prepared or studied. Ball milling, cryomilling and spray drying were used in this study to prepare partially and fully amorphous CIP for the first time. The physical characteristics were examined by PXRD, FTIR and DSC. CIP proved to be very difficult to amorphize, and only spray drying in pure water resulted in a fully amorphous product. It was discovered that while most processing methods resulted in the more stable zwitterionic form of the drug, spray drying in an ethanol/water mixture produced the unionized form. The zwitterion was found to convert to the unionized form upon heating to its melting point, whereas the reverse transformation occurred when unionized CIP was exposed to high humidity. This study thus provides insight into the proton transfer which can occur in a zwitterionic drug in the solid state, and the resultant changes to its crystal structure. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 Abstract Ciprofloxacin (CIP) can exist in two different forms: the zwitterion and the unionized form.While the crystal structure of each has been described independently, the ability of CIP to transform from one to the other in the solid state has not been described. The crystal structures of unionized and zwitterionic CIP were therefore compared using computational methods, including their packing arrangement, hydrogen bonding, packing energy, intermolecular potentials and HOMO/LUMO energy gap. The pure amorphous form of this drug has also never been prepared or studied. Ball milling, cryomilling and spray drying were used in this study to prepare partially and fully amorphous CIP for the first time. The physical characteristics, and in particular ionization state, of these samples were examined by PXRD, FTIR and DSC. Analysis of the crystal packing of unionized and zwitterionic CIP revealed that the presence of ionic interactions between the charged groups of the latter results in a denser and more stable crystal lattice. A greater HOMO/LUMO energy gap was also calculated for this sample, confirming its lower reactivity. CIP proved to be very difficult to amo...

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“…As for ciprofloxacin, the exposure of form I (anhydrous) to a relative humidity higher than 90% leads to the appearance of form II (hydrate), which is observed when an aqueous suspension of form I is prepared (Mafra et al, 2012).…”

Section: Cephalexin Erythromycin Ciprofloxacin Sulfamethoxazole Amentioning

confidence: 99%

Polymorphism: an evaluation of the potential risk to the quality of drug products from the Farmácia Popular Rede Própria

Santos

Reis

Jacon

et al. 2014

Braz. J. Pharm. Sci.

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Polymorphism in solids is a common phenomenon in drugs, which can lead to compromised quality due to changes in their physicochemical properties, particularly solubility, and, therefore, reduce bioavailability. Herein, a bibliographic survey was performed based on key issues and studies related to polymorphism in active pharmaceutical ingredient (APIs) present in medications from the Farmácia Popular Rede Própria. Polymorphism must be controlled to prevent possible ineffective therapy and/or improper dosage. Few mandatory tests for the identification and control of polymorphism in medications are currently available, which can result in serious public health concerns.Uniterms: Polymorphism. Medicines/quality control. Medicines/solubility. Medicines/bioavailability.O polimorfismo em sólidos é um fenômeno frequente em fármacos e pode levar a problemas na qualidade dos medicamentos por alterar suas propriedades físico-químicas, em especial a solubilidade e, consequentemente, a biodisponibilidade. Nesse trabalho realizou-se levantamento bibliográfico sobre os principais estudos e problemas relacionados ao polimorfismo em fármacos presentes nos medicamentos disponibilizados pela Farmácia Popular do Brasil. O polimorfismo deve ser controlado a fim de evitar possível ineficácia terapêutica e/ou dosagem inapropriada dos medicamentos. Destacamos que são poucos os ensaios obrigatórios para identificação e controle desse fenômeno em medicamentos, o que pode acarretar grande problema de saúde pública. Unitermos:Polimorfismo. Medicamentos/controle de qualidade. Medicamentos/solubilidade. Medicamentos/biodisponibilidade.

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Packing Interactions in Hydrated and Anhydrous Forms of the Antibiotic Ciprofloxacin: a Solid-State NMR, X-ray Diffraction, and Computer Simulation Study

Cited by 126 publications

References 16 publications

Solid-State Organization and Ambipolar Field-Effect Transistors of Benzothiadiazole-Cyclopentadithiophene Copolymer with Long Branched Alkyl Side Chains

Solid-State Organization and Ambipolar Field-Effect Transistors of Benzothiadiazole-Cyclopentadithiophene Copolymer with Long Branched Alkyl Side Chains

Two Faces of Ciprofloxacin: Investigation of Proton Transfer in Solid State Transformations

Polymorphism: an evaluation of the potential risk to the quality of drug products from the Farmácia Popular Rede Própria

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