Hydration-Induced Proton Transfer in the Solid State of Norfloxacin

Hu, Ting‐Chou; Wang, Shunli; Chen, Ting-Fang; Lin, Shan‐Yang

doi:10.1002/jps.10136

Cited by 43 publications

(24 citation statements)

References 26 publications

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“…Similar results were obtained with norfloxacin, with the unionized drug 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 converting to the zwitterion when exposed to high humidity. This proton transfer was reversible upon heating above 155 o C. 61 Incorporation of water molecules has been found to lower the energy barrier for proton transfer, which enables this conversion to occur upon hydration. 62…”

Section: Physical Stability In Humid Conditionsmentioning

confidence: 98%

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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Section: Physical Stability In Humid Conditionsmentioning

confidence: 98%

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

Mesallati

Mugheirbi

Tajber

2016

Crystal Growth & Design

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“…6 This solid-state transformation can have significant effects on a variety of physical and chemical properties, and eventually modify the pharmaceutical properties, such as solubility, dissolution and bioavailability. 7,8 Thus, detection and understanding of the interactions of water and drugs is of utmost relevance in order to improve and control the quality of the final product.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, Raman spectroscopy has been successfully used for monitoring the hydration and dehydration processes of different sugars, such as glucose and cyclodextrins, [18][19][20][21][22][23][24] and pharmaceutical drugs. 7,[25][26][27][28] Theophylline [1,3-dimethyl-xanthine, hereafter named by TP ( Fig. 1)] is a natural derivative of xanthine found mainly in tea, which presents several pharmaceutical and medical applications, [29][30][31] and is included in the core essential medicines list of the World Health Organization (WHO).…”

Section: Introductionmentioning

confidence: 99%

Probing Pseudopolymorphic Transitions in Pharmaceutical Solids using Raman Spectroscopy: Hydration and Dehydration of Theophylline

Amado

Nolasco

Ribeiro‐Claro

2007

Journal of Pharmaceutical Sciences

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Theophylline is known to undergo vapor phase induced hydrate-anhydrate pseudopolymorphic transformations, which can affect its bioavailability. In this work, the kinetics of the pseudopolymorphic transitions of theophylline crystals in different storage conditions is studied using a vibrational spectroscopic technique. While the hydration is a single-step process with a half-life time of ca. 5 h, the dehydration occurs through a two-step mechanism. In addition, the phase stability of hydrate-anhydrate systems in different relative humidity (RH) conditions was probed. The critical RH for anhydrous teophylline was found to be at ca. 79%, while the critical RH for dehydration is ca. 30%. ß

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“…All the FTIR spectra were obtained at a 4 cm -1 resolution and at 100 scans. The components and relative compositions of each sample were estimated quantitatively within the 1740-1600 cm -1 region of FTIR spectra by a curve-fitting algorithm with a Gaussian-Lorenzian function (Cheng et al, 2008;Hu et al, 2002). The best curvefitting procedure was performed by iterative fits toward a minimum standard error.…”

Section: Curve-fitted Ftir Determinationmentioning

confidence: 99%

Thermodynamic Study of Grinding-Induced Loratadine Inclusion Complex Formation Using Thermal Analysis and Curve-Fitted FTIR Determination

Lin¹,

Lin²,

Lin³

et al. 2011

Thermodynamics - Physical Chemistry of Aqueous Systems

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Hydration-Induced Proton Transfer in the Solid State of Norfloxacin

Cited by 43 publications

References 26 publications

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

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

Probing Pseudopolymorphic Transitions in Pharmaceutical Solids using Raman Spectroscopy: Hydration and Dehydration of Theophylline

Thermodynamic Study of Grinding-Induced Loratadine Inclusion Complex Formation Using Thermal Analysis and Curve-Fitted FTIR Determination

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