Effect of grinding on the dehydration behavior of nedocromil sodium hydrates

Nedocromil sodium has a number of known hydrate states, a monohydrate, a trihydrate and a heptahemihydrate, including an amorphous state. Effect of grinding on the hydration states of nedocromil sodium crystals was studied. After grinding the trihydrate, heptahemihydrate was observed in the ground sample, even though, the water content in the ground sample was not sufficient to cover the heptahemihydrate’s hydration level. On the other hand, in the ground heptahemihydrate, trihydrate was existed. Apparent activation energies (ΔE) for hydrates, monohydrate→anhydrate, trihydrate→monohydrate and heptahemihydrate→amorphous(anhydrate), were calculated using TG data. ΔE for the dehydration of heptahemihydrate was significantly lower than that of other hydrates. Obtained ΔE data explained the inter-conversion behavior of nedocromil sodium induced by grinding.     

Effects of dehydration temperatures on moisture absorption and dissolution behavior of theophylline.

Anhydrous theophylline was prepared by heating theophylline monohydrate at temperatures between 60 degrees C and 140 degrees C. The effects of dehydration temperatures on the moisture absorption and dissolution behavior of anhydrous theophylline were investigated in this study. The hydration rate of anhydrous theophylline at 95% relative humidity and 25 degrees C decreased with increasing dehydration temperatures. From the fitting analysis of solid-state reaction models, the hydration reaction was found to be governed by the phase boundary reaction model for samples prepared at lower dehydration temperatures (<100 degrees C) but the reaction obeyed the growth of nuclei reaction model when samples were dehydrated at higher temperatures. The dissolution rates of various anhydrous theophylline samples were measured by the rotating disk method. The calculated solubility of anhydrous theophylline prepared by heating was about 2.5 times higher than that of theophylline monohydrate. The phase transformation rate from the anhydrous form to the monohydrate during dissolution tests decreased with higher dehydration temperatures. It was found that the anhydrous theophylline prepared at different dehydration temperatures transformed to the monohydrate by way of different growth of hydrate nuclei mechanism.     

The molecular mechanisms of plasticity in crystal forms of theophylline

Plastic and elastic behaviors of organic crystals have profound influence on the processability of pharmaceutical substances. Analogous to metals, the identifications of molecular slip planes in organic crystals are regarded as a strategy for harnessing plasticity. In this work, we experimentally characterized the form II anhydrous theophylline (THPa) and its monohydrate (THPm) for their distinct plastic and elastic behaviors. Extensive DFT calculations were performed to model the effects of increasing lattice strains on molecular packing. We discovered that the energy barrier associated with the strain-induced molecular rearrangement would link to the plasticity of THPa, and possibly other simple aromatic compounds. Meanwhile, water molecules in THPm disrupt the stacking architecture from THPm and effectively undermine the general mechanism for plasticity. Hydrate formation would therefore be an alternative strategy to engineer the mechanical property of organic crystalline materials.     

Chemical mapping of hydration and dehydration process of theophylline in tablets using terahertz pulsed imaging

The purpose of this research is to investigate the topographical pattern of hydration and dehydration (also known as pseudo-polymorphic change) of drug substance in drug product using terahertz (THz) pulsed imaging. Emphasis is placed on (1) applicability of THz pulsed imaging and (2) kinetic analysis in the pseudo-polymorphic change. Either anhydrous or monohydrated form of theophylline was used as the drug substance, leading to initially anhydrous or monohydrated tablets. These tablets were stored at 25°C to keep the relative humidity constant at 84% (anhydrous tablets) or 45% (monohydrated tablets), respectively. The THz pulsed imaging was confirmed to enable visualization that the hydration of the anhydrous form or the dehydration of the monohydrated form began on the surface of the tablets and gradually progressed to the core side in the tablets with storage. Kinetic studies indicated that these pseudo-polymorphic changes followed the phase boundary mechanism. Since the other imaging techniques has been scarcely achieved to show the topographical pattern of pseudo-polymorphic change of drug substances in drug products directly and visually, it is considered that THz pulsed imaging has a potential ability to solve complicated issues in pharmaceutical development.     

Effect of thermal dehydration and rehydration on Na-magadiite structure

The effect caused by dehydration and rehydration of the synthetic Na-magadiite was investigated by TGA, XRD, SEM, and ²⁹Si NMR. Thermal analysis of Na-magadiite presented two well-defined loss mass stages between 20 and 150 °C and another between 270 and 310 °C, both related to the removal of interlayer water. The swelling behavior of Na-magadiite was studied by thermal dehydration data obtained at 150 and 300 °C, and respective rehydration by water addition. X-ray patterns showed that the dehydration of Na-magadiite at 150 and 300 °C provoked the basal spacing decrease. The XRD also showed that only the material treated at 150 °C returned to the original structure with the rehydration. ²⁹Si NMR spectra showed that after rehydration, the Q₃/Q₄ relationship presented the same value for Na-magadiite treated at 150 °C. However, this Q₃/Q₄ value decreased when the treatment was done at 300 °C. Kinetic studies of thermal decomposition showed that the dehydration of magadiite is based on a phase boundary-controlled reaction, caused by contracting areas. The exfoliation of lamellas with thermal treatment can explain this behavior, as observed in SEM images.     

Application of DTA for investigation of hydration and dehydration of crystal hydrates

The results of the investigation of the hydration processes of the dehydration products of magnesium carbonate trihydrate are shown. The DTA curve was used to calculate the functionQ(t). It was found that the results were in good agreement with the equation , whereQ is the heat evolved during the hydration timet;Q ₀,Q _f are the same for the initial and final products, respectively,k ₁ andk ₂ are the hydration constants.

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Zusammenfassung Die benutzte Methode wurde am Beispiel der Untersuchung des Hydrationsvorganges der Dehydratisierungsprodukte des Magnesiumkarbonat-Trihydrats demonstriert. Zur Errechnung der FunktionQ(t) dienten die DTA-Kurven. Die Ergebnisse folgten gut der Gleichung , woQ die freigesetzte Wärme während der Hydratationszeitt, Q ₀,Q _f dieselbe für die Anfangs- und Endprodukte,k ₁,k ₂ die Hydratationskonstanten bedeuten.

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Résumé Pour illustrer la méthode employée, on communique les résultats se rapportant à l'étude du phénomène d'hydration des produits de déshydratation du carbonate de magnésium trihydraté. On calcule la fonctionQ(t) à l'aide des courbes d'A.T.D. Les résultats obtenus sont en bon accord avec les valeurs de l'équation oùQ est la chaleur dégagée pendant le temps d'hydratationt, Q ₀ etQ _f sont les valeurs correspondantes pour les produits initiaux et finals,k ₁ etk ₂ les constantes d'hydratation.

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. Q(t) (). , , ,t,Q ₀ Q _f — , ,k ₁ k ₂ — .

     

Dependence of kinetics of copper sulfate pentahydrate dehydration on water vapor pressure

The dependence of the growth rate v_g of nuclei during CuSO₄·5H₂O dehydration upon water vapor pressure P_H2O has been investigated. At small P_H2O (less than 1 Torr at 50°C), v_g falls rapidly with decreasing P_H2O, and simultaneously v_g anisotropy disappears. At P_H2O = 1–9 Torr, v_g for elliptic and round nuclei is constant and independent of P_H2O. The influence of initially keeping the samples in water vapor upon the kinetics of the following dehydration has been studied. Treatment by water vapor leads to slowing of dehydration and increasing its degree of transformation. On the basis of data obtained a kinetic interpretation of the Topley-Smith effect has been proposed.     

Adsorption of water vapor on ZnO: Effects of annealing and grinding

TG, DTA, and DTGA study of water vapor adsorption on ZnO showed that the water vapor was adsorbed reversibly at 500°C (0.12 mg/g ZnO). Irreversible desorption of water vapor was also found at approximately 270°C. Both the specific surface area and the amount of water vapor adsorbed reversibly decreased with increasing annealing temperature above 500°C. When as-received ZnO was ground, the amount of water vapor adsorbed reversibly decreased sharply before any significant change took place in the specific surface area. At longer grinding time, the specific surface area increased but the amount of water vapor adsorbed reversibly increased only slightly with the grinding time. When the specimen was ground after annealing, the reversible adsorption of water vapor was not affected by the thermal history before grinding.     

Effect of thermal dehydration on surface characteristics of titania gel

The surface properties of titania gel and its thermal dehydration products were investigated by nitrogen and water vapour sorption between 110 and 600°C. Structural and phase changes were studied by X-ray diffractometry and differential thermal analysis. Up to 200°C, samples were X-ray amorphous and formed anatase at 300, 450 and 600°C. The glow phenomenon is attributed to the conversion to anatase at 350°C.Thermal dehydration of the gel between 110 and 300°C and 600°C led to the widening of the pore radii of the gel. At 450°C, marked steps appeared on the nitrogen isotherm, and was accompanied by a sharp increase in nitrogen uptake. The stepwise character is attributed to the presence of a certain porosity characteristic of the gel.Heats of immersion in water depend mainly on the hydrophilic centres on the surface, whereas heats of immersion in cyclohexane are controlled by the micropore fraction of the gel.     

The interaction of the theophylline metastable phase with water vapor

The conditions of hydration of the stable and metastable theophylline phases were determined. Two-phase metastable phase/monohydrate and stable phase/monohydrate equilibrium pressures were measured at 25, 30, and 35°C. The metastable phase began to react with water vapor at lower relative humidities than the stable phase. Processes that occurred with the metastable and stable theophylline phases over various water pressure ranges were considered. The metastable phase exhibited an unusual behavior at 25°C and relative humidity 47%. At constant water vapor pressure and temperature, theophylline was initially hydrated and then lost water and again became anhydrous. Two consecutive processes occurred in the system, the formation of theophylline monohydrate from the metastable phase and its decomposition to the stable phase. The ratio between the rates of these processes determined the content of the monohydrate at the given time moment.     

Effect of grinding on thermal reactivity of ceramic clay minerals

The effect of grinding on thermal behavior of pyrophyllite and talc as commonly used ceramic clay minerals was investigated by DTA, TG, emanation thermal analysis (ETA), B.E.T. surface area (s.a.) measurements, X-ray diffraction (XRD) and scanning electron microscopy (SEM). A vibratory mill was used in this study, grinding time was 5 min. It was found that the grinding caused an increase in surface area and a grain size reduction of the samples. From TG and DTA results it followed that grinding caused a decrease of the temperature at which the structure bound OH groups released. The formation of high temperature phases was enhanced with the ground samples. For the ground talc sample the crystallization of non-crystalline phase into orthorhombic enstatite was observed in the range of 800°C. For ground pyrophyllite a certain agglomeration of grains was observed in the range above 950°C. Moreover, for both clays the ETA characterized a closing up of subsurface irregularities caused by grinding as a decrease of the emanation rate in the range 250–400°C. The comparison of thermal analysis results with the results of other methods made it possible to better understand the effect of grinding on the ceramic clays.     

Effect of structure on the mechanism of dehydration of clay minerals

The kinetics of the isothermal dehydration of two clay minerals, attapulgite and powdered vermiculite were studied both in vacuo and in the presence of constant water vapour pressure. The mechanism of dehydration was found to be interfacial where diffusion plays a dominant role and it is called “activated diffusion”. A comparison is made with some layered structure clay minerals.     

Effect of deuteration on the thermal dehydration of lithium sulfate monohydrate

Effects of deuteration on the thermal stability, enthalpy change and kinetic parameters for the thermal dehydration of Li₂SO₄·H₂O were examined by means of TG and DSC. The enthalpy change for the monohydrate was smaller by 1.63±0.75 kJ/mol than that for the monodeuterate. The rate constant for the monohydrate was a little larger than that for the monodeuterate. However, the thermal stability, activation energy and frequency factor were practically unaffected by deuteration of the hydrate. It is suggested that the activation entropy as well as the activation energy should be considered in explaining the kinetic deuterium isotope effect in the thermal dehydration of Li₂SO₄·H₂O.

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Zusammenfassung Die Wirkung der Deuterisierung auf die Thermostabilität, die Enthalpie-Änderungen und kinetischen Parameter der thermischen Dehydratisierung von Li₂SO₄·H₂O wurden durch TG und DSC untersucht. Die Enthalpie-Änderung für das Monohydrat wurde um 1.63±0.75 kJ/mol niedriger gefunden als für das Monodeuterat. Die Geschwindigkeitskonstante für das Monohydrat war etwas größer als für das Monodeuterat. Die Thermostabilität, die Aktivierungsenergie und der Frequenzfaktor wurden jedoch von der Deuterisierung des Hydrats praktisch nicht beeinflußt. Es wird vorgeschlagen, daß bei der Erklärung des kinetischen Deuterium-Isotop-Effekts bei der thermischen Dehydratisierung von Li₂SO₄·H₂O sowohl die Aktivierungsentropie als auch die Aktivierungsenergie berücksichtigt werden müssen.

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, Li₂SO₄·H₂O. 1.63+0.75 /. , . , , . , Li₂SO₄·H₂O.