Challenges in the development of hydrate phases as active pharmaceutical ingredients – An example

Feth, Martin P.; Nagel, Norbert; Baumgärtner, B.; Bröckelmann, Martin; Rigal, David; Otto, Bernhard; Spitzenberg, Michael; Schulz, Markus; Becker, Bernd; Fischer, F.T.; Petzoldt, Christine

doi:10.1016/j.ejps.2010.11.001

Cited by 27 publications

(20 citation statements)

References 23 publications

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“…In case of the first ones, FT-IR shows sharp OH-bands at relatively low frequencies, while in TGA, rather wide weight loss ranges are observed, and DSC presents broad endothermic peaks. On the contrary, ion isolated hydrates are characterized by sharp dehydration endotherms in DSC and narrow weight loss ranges in TGA [ 61 , 62 ].…”

Section: Methods Applied For Analysis Of Hydratesmentioning

confidence: 99%

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Pharmaceutical Hydrates Analysis—Overview of Methods and Recent Advances

et al. 2020

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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.

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Section: Methods Applied For Analysis Of Hydratesmentioning

confidence: 99%

“…A separate group of hydrates form hydrated co-crystals, which are quite common among obtained forms of APIs. Despite being more complex than simple hydrates, their analysis unfolds with application of the same methods [ 62 , 110 , 111 , 112 , 113 , 114 , 115 ].…”

Section: Hydrates Structural Analysis Selected Cases Within the Lmentioning

confidence: 99%

Pharmaceutical Hydrates Analysis—Overview of Methods and Recent Advances

et al. 2020

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“…Ion‐associated water and isolated water are included in the crystal lattice in a fixed stoichiometry, whereas channel water usually exists nonstoichiometrically and can be troublesome in changing to various ratios of hydrates . Hydration and dehydration events can occur in response to changes in the environment conditions or to thermal or humidity variation during the manufacturing processes . These form transformations subsequently alter the physical and chemical properties of the APIs including bulk density, morphology, color, melting point, surface energy, and viscosity .…”

Section: Introductionmentioning

confidence: 99%

Solid‐State Characterization and Transformation of Various Creatine Phosphate Sodium Hydrates

Jiang

Zhang

et al. 2014

Journal of Pharmaceutical Sciences

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“…However, the picture can be more complex. For example, an SGLT1 inhibitor has been reported to display a combination of stoichiometric and nonstoichiometric hydrates . An alternative classification system for different types of hydrates has been described based on the general structural differences of the water networks…”

Section: Introductionmentioning

confidence: 99%

“…For example, an SGLT1 inhibitor has been reported to display a combination of stoichiometric and nonstoichiometric hydrates. 13 An alternative classification system for different types of hydrates has been described based on the general structural differences of the water networks. 14 In the case of BMS-663068-01 free acid, single-crystal data with associated X-ray diffraction (XRD) indicated that there were changes in unit cell dimensions on conversion from the anhydrous form II to the hydrate form III, with the water being located in distinct channels within the crystal lattice.…”

Section: Introductionmentioning

confidence: 99%