Thermal Dehydration of Nafagrel Hydrochloride Hydrate at Controlled Water Vapor Partial Pressures.

Kitaoka, Hiroaki; Ohya, Kazumi; Hakusui, Hideo

doi:10.1248/cpb.43.1744

Cited by 10 publications

(3 citation statements)

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“…The effect of external vapor pressure has been noted elsewhere. 12 At slower scan rates the dehydration events occurred at progressively lower temperatures. This result was likely because of less thermal lag in the DSC measurement and changes in the vapor pressure inside the DSC sample pan at the slower scan rates.…”

Section: Discussionmentioning

confidence: 98%

Solid-State Characterization of Paclitaxel

Liggins

Hunter

Burt

1997

Journal of Pharmaceutical Sciences

202

126

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The purpose of this work was to characterize the solid-state properties of anhydrous paclitaxel and paclitaxel dihydrate. Paclitaxel I (anhydrous) was suspended in water for 24 h to convert it to paclitaxel.2H2O. Both forms were analyzed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). X-ray powder diffraction (XRPD) patterns were obtained at 25, 100, and 195 degrees C. Dissolution profiles of both forms were obtained in water at 37 degrees C over h. DSC of paclitaxel.2H2O showed two endothermic peaks below 100 degrees C, corresponding to dehydration. The resulting solid phase was termed "dehydrated paclitaxel.2H2O". At 168 degrees C, a solid-solid transition was observed in which dehydrated paclitaxel.2H2O was converted to a semicrystalline material called "paclitaxel I/am". The solid-solid transition was followed by melting at 220 degrees C. TGA of paclitaxel.2H2O showed a corresponding biphasic weight loss below 100 degrees C, which was equivalent to the weight of 2 mol of water. DSC of paclitaxel I showed no transitions before melting at 220 degrees C, and no weight loss was observed by TGA. Quenching of paclitaxel I from the melt produced amorphous paclitaxel with a glass transition at 152 degrees C. XRPD confirmed that paclitaxel I, paclitaxel.2H2O, and dehydrated paclitaxel.2H2O had different crystal structures. The X-ray patterns of paclitaxel I and paclitaxel I/am were similar, however the two forms of paclitaxel did not behave identically when analyzed by DSC. The bulk dissolution studies with paclitaxel I showed a rapid increase in concentration to 3 micrograms/mL in 4 h, which decreased to 1 microgram/mL after 12 h, corresponding to the solubility of paclitaxel.2H2O. The solubility of paclitaxel.2H2O was 1 microgram/mL. The data demonstrate the existence of a dihydrate form of paclitaxel that is the stable form in equilibrium with water at 37 degrees C but which dehydrates at temperatures > 45 degrees C.

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Section: Discussionmentioning

confidence: 98%

Solid-State Characterization of Paclitaxel

Liggins

Hunter

Burt

1997

Journal of Pharmaceutical Sciences

202

126

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“…1) In a preformulation study, hygroscopicity of API is routinely investigated because moisture sorption and desorption may induce crystal transformation into another crystalline form, [2][3][4] and different crystalline forms may affect various properties of pharmaceutics, e.g. solubility, bioavailability and stability.…”

mentioning

confidence: 99%

“…These remain almost a constant independent of relative humidities (RHs) or show steep weight change accompanied with crystal transformation by absorption or release of water molecules at critical relative humidities. 2,4) STFX hydrate showed unusual hygroscopicity. Water content of STFX hydrate changes gradually from dihydrate through sesquihydrate depending on RHs, while it exhibits almost the same X-ray powder diffraction patterns independent of RHs.…”

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confidence: 99%

Characterization of Non-stoichiometric Hydration and the Dehydration Behavior of Sitafloxacin Hydrate

et al. 2012

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Sitafloxacin (STFX) hydrate is a non-stoichiometric hydrate. The hydration state of STFX hydrate varies non-stoichiometrically depending on the relative humidity and temperature, though X-ray powder diffraction (XRPD) of STFX hydrate was not affected by storing at low and high relative humidities. The detailed properties of crystalline water of STFX hydrate were estimated in terms of hygroscopicity, thermal analysis combined with X-ray powder diffractometry, crystallography and density functional theory (DFT) calculation. STFX hydrate changed the water contents continuously and reversibly from an equivalent amount of dihydrate through that of sesquihydrate depending on the relative humidity at 25°C. Thermal analysis and X-ray powder diffraction (XRPD) simultaneous measurement also revealed that STFX hydrate dehydrated into a hydrated state equivalent to monohydrate by heating up to 100°C, whereas XRPD patterns were slightly affected. This indicated that the crystal structure of STFX hydrate was retained at the dehydration level of monohydrate. Single-crystal X-ray structural analysis showed that two STFX molecules and four water molecule sites were contained in an asymmetric unit. STFX molecules formed a channel structure where water molecules were included. At the partially dehydrated state, at least two of four water molecules were considered to be disordered in occupancy and/or coordinates. Insight into the crystal structure of STFX hydrate stored at low and high relative humidities and geometry of the hydrogen bond were helpful to estimate the origin of non-stoichiometric hydration of STFX hydrate.

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