Influence of Temperature on Solvent-Mediated Anhydrate-to-Hydrate Transformation Kinetics (original) (raw)
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Factors affecting crystallization of hydrates
Journal of Pharmacy and Pharmacology, 2010
Objectives To provide a comprehensive understanding of the competing thermodynamic and kinetic factors governing the crystallization of various hydrate systems. The ultimate goal is to utilize this understanding to improve the control over the unit operations involving hydrate formation, as well as to optimize the bioavailability of a given drug product. Key findings The thermodynamic and kinetic factors that govern hydrate crystallization are introduced and the current status of the endeavour to gain a mechanistic understanding of the phenomena that occur during the crystallization of different hydrate systems is discussed. The importance of hydrate investigation in the pharmaceutical field is exemplified by examining two specific hydrate systems: the polymorphic hydrate system and hydrates of pharmaceutical salts. Summary This review identifies the factors that are of critical importance in the investigation of anhydrate/hydrate systems. This knowledge can be used to control the phase transformation during pharmaceutical processing and storage, as well as in building a desired functionality for the final formulation.
Formation and Transformation Behavior of Sodium Dehydroacetate Hydrates
Molecules, 2016
The effect of various controlling factors on the polymorphic outcome of sodium dehydroacetate crystallization was investigated in this study. Cooling crystallization experiments of sodium dehydroacetate in water were conducted at different concentrations. The results revealed that the rate of supersaturation generation played a key role in the formation of the hydrates. At a high supersaturation generation rate, a new sodium dehydroacetate dihydrate needle form was obtained; on the contrary, a sodium dehydroacetate plate monohydrate was formed at a low supersaturation generation rate. Furthermore, the characterization and transformation behavior of these two hydrated forms were investigated with the combined use of microscopy, powder X-ray diffraction (PXRD), Raman spectroscopy, Fourier transform infrared (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and dynamic vapor sorption (DVS). It was found that the new needle crystals were dihydrated and hollow, and they eventually transformed into sodium dehydroacetate monohydrate. In addition, the mechanism of formation of sodium dehydroacetate hydrates was discussed, and a process growth model of hollow crystals in cooling crystallization was proposed.
International Journal of Greenhouse Gas Control, 2014
Most hydrate that forms or dissociates are in situations of constant non-equilibrium. This is due to the boundary conditions and Gibbs Phase rule. At a minimum this leaves a hydrate with two adsorbed phases in addition to hydrate and fluids. One adsorbed phase is governed by the mineral surfaces and the other by the hydrate surface. With pressure and temperature defined by local conditions, hydrate formation will never be able to reach any state of equilibrium. The kinetics of hydrate formation and dissociation are a complex function of competing phase transitions. This requires kinetic theories that include minimization of free energy under constraints of mass and energy transport. Since phase transitions also change density, further constraints are given by fluid dynamics. In this work, we describe a new approach for nonequilibrium theory of hydrates together with a Phase Field Theory for simulation of phase transition kinetics. We choose a three component system of water, methane and carbon dioxide for illustration. Conversion of methane hydrate into carbon dioxide hydrate is a win-win situation of energy production combined with safe long term storage of carbon dioxide. Carbon dioxide is able to induce and proceed with a solid-state exchange, but is slow due to mass transport limitations. A faster process is the formation of new hydrate from injected carbon dioxide and residual pore water. This formation releases substantial heat. This assists in dissociating in situ methane hydrate, making the conversion progress substantially faster, because heat transport is very rapid in these systems. But conversion of liquid water into carbon dioxide hydrate, in the vicinity of the hydrate core will increase temperatures to some portions of the surface. The dissociating regions of the methane hydrate core will show a local decrease in temperature, due to extraction of heat for methane hydrate dissociation from surroundings. Another reason for heat transport implementation is that regions of the system that contains non-polar gas phase will have low heat conductivity and low heat convection. At this stage we apply a simplified heat transport model in which "lumped" efficient heat conductivity is used. We illustrate the theory on the conversion of methane hydrate to mix methane-carbon dioxide hydrate using three initial hydrate sizes: 150Å × 150Å, 500Å × 500Å and 5000Å × 5000Å. The hydrate cores used are spherical because it makes it easier to illustrate the impact of curvature. Symmetrical aspects simplifies the dependency to a two dimensional problem -although there are no such limitations in theory. The mineral surfaces are considered to be water wetting in these examples. It was observed that the smaller sizes convert to a more unstable mix hydrate for some periods of the simulation time, during which there were significant losses of the initial methane hydrate core. These instabilities are caused by local under saturated fluid phases around the hydrate core. Eventually a steady state progress was observed. The largest size system appeared to reach a steady state situation comparable faster than the two smaller systems.
Rapid conversion of API hydrates to anhydrous forms in aqueous media
Journal of Pharmaceutical Sciences, 2009
Three anhydrous polymorphs, a monohydrate and a dihydrate of an active pharmaceutical ingredient, N-{[(5S)-3-(4-{6-[(1R,5S)-6-cyano-3-oxabicyclo[3.1.0]hex-6yl]pyridin-3-yl}phenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide (Compound 1), have been crystallized and characterized. Slurry experiments and thermal data have been used to determine their relative thermodynamic stability. The hydrates of Compound 1 were found to be less stable than the most stable anhydrous Form I and converted into Form I in water within 15 min. The rate of conversion in a dry state was found to depend on the relative humidity (RH) and was highest at the two RH extremes examined, 5% and 97.5% RH.
Identification of phase boundaries in anhydrate/hydrate systems
Journal of Pharmaceutical Sciences, 2007
Near-infrared spectroscopy was used to monitor the phase conversion for two solvatomorphs of caffeine, an anhydrous form and a nonstoichiometric hydrate, as a function of time, temperature, and relative humidity. The transformation kinetics between these caffeine forms was determined to increase with temperature. The rate of conversion was also determined to be dependent on the difference between the observed relative humidity and the equilibrium water activity of the anhydrate/hydrate system, that is, phase boundary. Near the phase boundary, minimal conversion between the anhydrous and hydrated forms of caffeine was detected. Using this kinetic data, the phase boundary for these forms was determined to be approximately 67% RH at 108C, 74.5% RH at 258C, and 86% RH at 408C. At each specified temperature, anhydrous caffeine is the thermodynamically stable form below this relative humidity and the hydrate is stable above. The phase boundary data were then fitted using a second order polynomial to determine the stability relationship between anhydrous caffeine and its hydrate at additional temperatures. This approach can be used to rapidly determine the stability relationship for solvatomorphs as well as the relative kinetics of their interconversion. Both of these factors are critical in selecting the development form, designing appropriate stability studies, and developing robust conditions for the preparation and packaging of the API and formulated drug product. ß
Driving force for crystallization of gas hydrates
Journal of Crystal Growth, 2002
A general expression is derived for the supersaturation for crystallization of one-component gas hydrates in aqueous solutions. The supersaturation is the driving force of the process, since it represents the difference between the chemical potentials of a hydrate building unit in the solution and in the hydrate crystal. Expressions for the supersaturation are obtained for solutions supersaturated in isothermal or isobaric regime. The results obtained are applied to the crystallization of hydrates of methane, ethane and other one-component gases. r
Journal of Molecular Graphics & Modelling, 2022
In this paper we report a successful molecular simulation study exploring the heterogeneous crystal growth of sI methane hydrate along its [001] crystallographic face. The molecular modeling of the crystal growth of methane hydrate has proven in the past to be very challenging, and a reasonable framework to overcome the difficulties related to the simulation of such systems is presented. Both the microscopic mechanisms of heterogeneous crystal growth as well as interfacial properties of methane hydrate are probed. In the presence of the appropriate crystal template, a strong tendency for water molecules to organize into cages around methane at the growing interface is observed; the interface also demonstrates a strong affinity for methane molecules. The maximum growth rate measured for a hydrate crystal is about 4 times higher than the value previously determined for ice I in a similar framework (
Journal of Pharmaceutical Sciences, 2007
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
An insight into water of crystallization during processing using vibrational spectroscopy
Journal of Pharmaceutical Sciences, 2009
Many organic molecules used as drugs can incorporate water into their crystal lattice. These compounds are also prone to processing-induced transformations (PITs) because processing often exposes the compounds to moisture, heat and mechanical stress. The aim of this review is to provide an overview of the possibilities for following and understanding hydrate/anhydrate transformations using vibrational spectroscopy (mid-infrared, near-infrared, Raman and terahertz). The review begins with a general section on hydrates, followed by considerations on the impact of these on drug products and a description of transformation mechanisms of hydrates. Moreover, a general introduction is given for the spectroscopic techniques together with a discussion of critical issues for quantification models. Unit operations that may induce transformations in hydrate systems are discussed with focus on the published work on the use of spectroscopy to derive information from these processes. Finally, the effect of excipients on PITs is discussed. ß