Abstract
Crystalline solids can incorporate water molecules into their crystal lattice causing a dramatic impact on their properties. This explains the increasing interest in understanding the dehydration pathways of these solids. However, the classical thermal analytical techniques cannot spatially resolve the dehydration pathway of organic hydrates at the single particle level. We have developed a new method for imaging the dehydration of organic hydrates using Raman line-focus microscopy during heating of a particle. Based on this approach, we propose a new metastable intermediate of theophylline monohydrate during the three-step dehydration process of this system and further, we visualize the complex nature of the three-step dehydration pathway of nitrofurantoin monohydrate to its stable anhydrous form. A Raman line-focus mapping option was applied for fast simultaneous mapping of differently sized and shaped particles of nitrofurantoin monohydrate, revealing the appearance of multiple solid-state forms and the non-uniformity of this particle system during the complex dehydration process. This method provides an in-depth understanding of phase transformations and can be used to explain practical industrial challenges related to variations in the quality of particulate materials.
Highlights
Interactions of water with solids are critical for most materials and can have a dramatic impact on their functionality[1]
The shape of the differential scanning calorimetry (DSC) thermogram from theophylline monohydrate (TP MH) is suggesting that the dehydration process is a two-step process[17]
We demonstrated experimentally that Raman line-focus microscopy can be used to investigate different crystalline solid-state transformations and reveal metastable intermediates that are of pharmaceutical relevance at the single particle level
Summary
Interactions of water with solids are critical for most materials and can have a dramatic impact on their functionality[1]. The dehydration of an organic hydrate, when exposed to an external stress such as temperature, pressure or humidity, can result in a mixture of solid-state forms making it challenging to reveal and track metastable intermediates[4]. This has inspired the development of several mechanistic schemes[5] for the classification of hydrates and most notably among them is the Rouen 96 model by Petit and Coquerel[6]. We employ multivariate curve resolution (MCR)[14,15] and non-negative least squares (NNLS) in the data analysis in order to reveal their metastable solid-state intermediates, and to determine the dehydration pathways of TP MH and NF MH II
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