Dehydration mechanism of a small molecular solid: 5-nitrouracil hydrate

Abstract

Previous studies of the dehydration of 5-nitrouracil (5NU) have resulted in it being classified as a ‘‘channel\ud hydrate’’ in which dehydration proceeds principally by the exit of the water molecules along channels in\ud the structure. We have re-examined this proposal and found that in fact there are no continuous channels\ud in the 5NU structure that would contribute to such a mechanism. Product water molecules would be\ud immediately trapped in unlinked voids in the crystal structure and would require some additional\ud mechanism to break loose from the crystal. Through a detailed structural analysis of the macro and micro\ud structure of the 5NU as it dehydrates, we have developed a model for the dehydration process based on\ud the observed development of structural defects in the 5NU crystal and the basic crystallography of the\ud material. The model was tested against standard kinetic measurements and found to present a satisfactory\ud account of kinetic observations, thus defining the mechanism. Overall, the study shows the necessity of\ud complementing standard kinetic studies with a parallel macro and micro examination of the dehydrating\ud material when evaluating the mechanisms of dehydration and decomposition processes

Effect of Experimental and Sample Factors on Dehydration Kinetics of Mildronate Dihydrate: Mechanism of Dehydration and Determination of Kinetic Parameters

“…As already mentioned, it has been observed that the dehydration kinetic parameters can be strongly affected by various sample and experimental factors . Differences of the sample particle size, crystal habit, sample history, and crystal defect distribution can result in different dehydration rates, E a variation, and even change the kinetic model. Besides these factors, all the mentioned kinetic parameters can be affected by the relative humidity, inert gas flow rate, and sample weight .…”

“…[25][26][27] Differences of the sample particle size, [28][29][30][31][32] crystal habit, 33 sample history, 25 and crystal defect distribution 24 can result in different dehydration rates, E a variation, and even change the kinetic model. Besides these factors, all the mentioned kinetic parameters can be affected by the relative humidity, 31,32,[34][35][36] inert gas flow rate, 31,34 and sample weight. 28,37 Thus, for the better understanding of the dehydration process and calculated kinetic parameters, the effects of sample and experimental factors should be evaluated.…”

Two New Polymorphs of Huperzine A Obtained from Different Dehydration Processes of One Monohydrate

“…Polymorphism occurs commonly among drugs and different polymorphs always present distinct physical and chemical attributes, such as compressibility, melting point, crystal habit, color, density, dissolution rate, and solubility. − Accordingly, in order to explore the polymorphism landscape and to optimize the solid-state properties, thorough polymorph screening and solid-state characterization of drug candidates are routinely conducted throughout the drug development process. − The most common polymorph screening methods are crystallization from melt, vapor and cooling, evaporating, antisolvent, and slurrying with different solvents and at different temperatures. In addition, dehydration is an effective method for polymorph screening − and some polymorphs can be prepared only by this conversion …”

Tracking Dehydration Mechanisms in Crystalline Hydrates with Molecular Dynamics Simulations

“…Different mechanistic descriptions of dehydration such as nucleation and growth and 1D/2D/3D diffusion have led to the development of kinetic models, which are usually empirically fitted to experimental data such as thermal gravimetric analysis (TGA) data. Again, the results are often not suitable to discriminate between different dehydration models since many of them fit the data equally well. , …”

“…Again, the results are often not suitable to discriminate between different dehydration models since many of them fit the data equally well. 5,6 Theoretical techniques can be used to obtain a great deal of insight into the energetics and related properties of crystalline materials. 7−10 Common density functional theory (DFT) simulations are not the most suitable computational approach to effectively probe the mechanistic aspect of hydration, as they typically can only be used to determine the energies of the lowest energy structures.…”