Abstract
This review discusses a set of instrumental and computational methods that are used to characterize hydrated forms of APIs (active pharmaceutical ingredients). The focus has been put on highlighting advantages as well as on presenting some limitations of the selected analytical approaches. This has been performed in order to facilitate the choice of an appropriate method depending on the type of the structural feature that is to be analyzed, that is, degree of hydration, crystal structure and dynamics, and (de)hydration kinetics. The presented techniques include X-ray diffraction (single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD)), spectroscopic (solid state nuclear magnetic resonance spectroscopy (ssNMR), Fourier-transformed infrared spectroscopy (FT-IR), Raman spectroscopy), thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)), gravimetric (dynamic vapour sorption (DVS)), and computational (molecular mechanics (MM), Quantum Mechanics (QM), molecular dynamics (MD)) methods. Further, the successful applications of the presented methods in the studies of hydrated APIs as well as studies on the excipients’ influence on these processes have been described in many examples.
Highlights
Polymorphism is a phenomenon defined as the possibility of one chemical substance to exist in several different crystallographic forms [1] depending on the temperature, pressure, and humidity as well as solvents applied during the crystallization process
This review aims to compare the analytical methods, both instrumental and computational, usually applied in active pharmaceutical ingredients (APIs) hydration studies
The difficulty of studies dealing with pharmaceutical hydrates lies in the fact that two different types of molecules are present in a crystal structure, namely API and water
Summary
Polymorphism is a phenomenon defined as the possibility of one chemical substance to exist in several different crystallographic forms [1] depending on the temperature, pressure, and humidity as well as solvents applied during the crystallization process. Hydrates show better compressibility and tabletability than anhydrates, are less affected by wet granulation process, and are less susceptible for the tablet storage conditions like temperature and relative humidity (RH) In such cases, it could be reasonable to find and produce the most stable API hydrate to prevent the form alteration during production or storage. Theophylline monohydrate exhibits better solubility in water than its anhydrous form [24] These cases indicate the variability in properties of hydrated APIs and necessity to perform comparative studies between the differently hydrated forms in each particular case. When properly employed, the ability of most of the APIs to form solid hydrates can be a unique opportunity to improve their stability, processability, or biopharmaceutical properties or even to patent a new solid state form, as in the case of polymorphs For these purposes, a detailed analysis of hydrated pharmaceuticals is essential. The aim of this study was, besides presenting the recent advances in this topic, to facilitate the choice of the proper analytical method when exploring the APIs’ hydrates
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