Effect of Dehydration on the Formation of Levofloxacin Pseudopolymorphs.

Kitaoka, Hiroaki; Wada, Chisa; Moroi, Reimei; Hakusui, Hideo

doi:10.1248/cpb.43.649

Cited by 39 publications

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“…A hydrated crystal is easily broken by heating and also upon storage at low relative humidities, leading to possible transformation into the anhydrous form by crystal lattice rearrangement. As a result, the drug substance may form the metastable state.Many hydrates of drug substances have been reported, for instance, carbamazepine, 11) theophylline, 12) tetracaine hydrochloride, 13) levofloxacin, 14) and diclofenac acid salts. …”

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Water Vapor Adsorption Behavior of Sodium Deoxycholate Anhydrous Forms

Ono

Anzai

Tozuka

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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During pharmaceutical development processes, various investigations of physicochemical properties of a drug substance are conducted in order to guarantee the efficacy and the stability of pharmaceutical products. It is well known that the physicochemical properties of drug substances are changed by influence of water vapor under high and low relative humidity conditions. 2-4)A compound holding stoichiometric solvent molecule incorporated within the crystal lattice is designated a solvate. In particular, when the solvent is water, the compound is termed a hydrate, which is the most common solvate of drug substances.5) Because the investigation of manufacturing and formulation processes are conducted with particular attention to the behavior of drug substance hydrate, the existence of the hydrate state has a major impact on the drug development process.6) Moreover, the reduction in bioavailability may occur as the solubility of hydrate in general is lower than that of anhydrous form. 7,8) There are many studies in which the behavior of the crystal water molecule is influenced by relative humidity.9,10) A compound tends to incorporate a water molecule in the crystal structure at high relative humidities, while a hydrate may release the water molecule from the crystal at low relative humidities. It is therefore very important that the effect of relative humidity on the interconversion between the hydrate and anhydrous forms are investigated.Studies of the process of hydration and dehydration are of significance in order to predict the stability of the drug substance. Many hydrated compounds are stabilized by formation of hydrogen bonding networks between water and the drug substance molecule. A hydrated crystal is easily broken by heating and also upon storage at low relative humidities, leading to possible transformation into the anhydrous form by crystal lattice rearrangement. As a result, the drug substance may form the metastable state.Many hydrates of drug substances have been reported, for instance, carbamazepine, 11) theophylline, 12) tetracaine hydrochloride, 13) levofloxacin, 14) and diclofenac acid salts. 15)Among them, the hydrated form exists in several possible hydration states. Tetracaine hydrochloride has hemi-, mono-, and tetrahydrate states, nafagrel hydrochloride has hemi-and monohydrate states, and norfloxacin has sesqui-and pentahydrate states. 16)Sodium deoxycholate (NaDC) containing steroid skeleton is a kind of cholic acid salts. It is known that NaDC forms a micelle, 17) gel, 18) and complex 19) with drugs. It is a white powder used as a supportive solubilizing agent in pharmaceutical formulation. D'Archivio et al. suggested the possibility that NaDC was stabilized by the formation of a tetrahydrate helix structure of NaDC with the four water molecules held rigid by the formation of ion-ion, ion-dipole interactions and hydrogen bonding. 20) Vold et al. presumed the existence of NaDC octahydrate by the investigation of the solubility curve of NaDC.21) However, their findings could not sufficie...

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“…Many hydrates of drug substances have been reported, for instance, carbamazepine, 11) theophylline, 12) tetracaine hydrochloride, 13) levofloxacin, 14) and diclofenac acid salts. 15) Among them, the hydrated form exists in several possible hydration states.…”

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confidence: 99%

Water Vapor Adsorption Behavior of Sodium Deoxycholate Anhydrous Forms

Ono

Anzai

Tozuka

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Kitaoka et al reported that the heating rate and gas flow rate influenced the formation of pseudopolymorphs in DSC measurement. 19) Therefore the effect of the atmospheric conditions on the DSC curve of the dihydrate was investigated to confirm that the peaks were reproducible. The DSC curves of the dihydrate under a nitrogen gas flow rate of 0-100 ml/min are shown in Fig.…”

Section: Thermal Properties Of Cs-834 Modificationsmentioning

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Physicochemical Analyses of Phase Transition and Dehydration Processes of a New Oral 1.BETA.-Methylcarbapenem Antibiotic Agent, CS-834.

Kobayashi

Fukuhara²,

Kawamoto³

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…[28][29][30][31] In fact, other quinolone antibacterial agents showing dehydration/hydration or polymorphism were reported. [32][33][34][35] Notably, color changes in APIs due to dehydration/hydration could potentially be used as a quality control method. 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 7…”

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Powder Structure Analysis of Vapochromic Quinolone Antibacterial Agent Crystals

Sakon

Sekine

Uekusa

2016

Crystal Growth & Design

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Pipemidic acid crystals were found to undergo a reversible color change upon exposure to acetonitrile vapor via dehydration/hydration transformations. The mechanistic aspects of these transformations and the crystalline color change were revealed using X-ray analysis and theoretical calculations. ABSTRACTVapochromic materials, or those that show a reversible color change induced by vapor, are expected to serve as valuable sensors for volatile organic compounds (VOC) or humidity.Crystals of pipemidic acid (PPA), a quinolone antibacterial agent, were found to exhibit vapochromism, as they undergo a reversible color change in the presence of acetonitrile vapor.The colorless trihydrate phase transformed into a yellow anhydrous phase upon exposure to acetonitrile vapor, and returned to the trihydrate phase under high humidity. Ab initio structure determination from powder diffraction and solid state 13 C-NMR measurements revealed that the molecule exists in its zwitterionic form in the colorless trihydrate phase, whereas it is nonzwitterionic in the anhydrous phase because of the rearrangement of hydrogen bonds, due to dehydration in the crystal state. Theoretical calculations revealed that the color change in PPA is due to the change in the molecular electronic state upon taking the non-zwitterionic form, which generates a new HOMO state, thus leading to a HOMO-LUMO transition with a lower energy.

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Effect of Dehydration on the Formation of Levofloxacin Pseudopolymorphs.

Cited by 39 publications

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Water Vapor Adsorption Behavior of Sodium Deoxycholate Anhydrous Forms

Water Vapor Adsorption Behavior of Sodium Deoxycholate Anhydrous Forms

Physicochemical Analyses of Phase Transition and Dehydration Processes of a New Oral 1.BETA.-Methylcarbapenem Antibiotic Agent, CS-834.

Powder Structure Analysis of Vapochromic Quinolone Antibacterial Agent Crystals

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