| People | Locations | Statistics |
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| Naji, M. |
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| Motta, Antonella |
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| Aletan, Dirar |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Taccardi, Nicola |
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| Kononenko, Denys |
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| Petrov, R. H. | Madrid |
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| Alshaaer, Mazen | Brussels |
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| Bih, L. |
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| Casati, R. |
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| Muller, Hermance |
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| Kočí, Jan | Prague |
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| Šuljagić, Marija |
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| Kalteremidou, Kalliopi-Artemi | Brussels |
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| Azam, Siraj |
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| Ospanova, Alyiya |
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| Blanpain, Bart |
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| Ali, M. A. |
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| Popa, V. |
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| Rančić, M. |
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| Ollier, Nadège |
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| Azevedo, Nuno Monteiro |
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| Landes, Michael |
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| Rignanese, Gian-Marco |
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Zhao, Min
Queen's University Belfast
in Cooperation with on an Cooperation-Score of 37%
Topics
Publications (10/10 displayed)
- 2023The effects of surfactants on the performance of polymer-based microwave-induced in situ amorphizationcitations
- 2022Stabilizing Mechanisms of β-Lactoglobulin in Amorphous Solid Dispersions of Indomethacincitations
- 2021Investigation into the role of the polymer in enhancing microwave-induced in situ amorphizationcitations
- 2021Investigation into the role of the polymer in enhancing microwave-induced in situ amorphizationcitations
- 2017Solid state characterisation and taste masking efficiency evaluation of polymer based extrudates of isoniazid for paediatric administrationcitations
- 2015Generation of hydrate forms of paroxetine HCl from the amorphous state: an evaluation of thermodynamic and experimental predictive approachescitations
- 2014The influence of drug physical state on the dissolution enhancement of solid dispersions prepared via hot-melt extrusion: A case study using olanzapinecitations
- 2014An investigation into the dehydration behavior of paroxetine HCl form i using a combination of thermal and diffraction methods: The identification and characterization of a new anhydrous formcitations
- 2012Identification and characterization of stoichiometric and nonstoichiometric hydrate forms of paroxetine HCl: Reversible changes in crystal dimensions as a function of water absorptioncitations
- 2012Development of fully amorphous dispersions of a low Tgdrug via co-spray drying with hydrophilic polymerscitations
Places of action
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article
Identification and characterization of stoichiometric and nonstoichiometric hydrate forms of paroxetine HCl: Reversible changes in crystal dimensions as a function of water absorption
Abstract
Paroxetine hydrochloride (HCl) is an antidepressant drug, reported to exist in the anhydrous form (form II) and as a stable hemihydrate (form I). In this study, we investigate the hydration behavior of paroxetine HCl form II with a view to understanding both the nature of the interaction with water and the interchange between forms II and I as a function of both temperature and water content. In particular, we present new evidence for both the structure and the interconversion process to be more complex than previously recognized. A combination of characterization techniques was used, including thermal (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)), spectroscopic (attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR)), dynamic vapor sorption (DVS) and X-ray powder diffraction (XRPD) with variable humidity, along with computational molecular modeling of the crystal structures. The total amount of water present in form II was surprisingly high (3.8% w/w, 0.8 mol of water/mol of drug), with conversion to the hemihydrate noted on heating in hermetically sealed DSC pans. XRPD, supported by ATR-FTIR and DVS, indicated changes in the unit cell dimensions as a function of water content, with clear evidence for reversible expansion and contraction as a function of relative humidity (RH). Based on these data, we suggest that paroxetine HCl form II is not an anhydrate but rather a nonstoichiometric hydrate. However, no continuous channels are present and, according to molecular modeling simulation, the water is moderately strongly bonded to the crystal, which is in itself an uncommon feature when referring to nonstoichiometric hydrates. Overall, therefore, we suggest that the anhydrous form of paroxetine HCl is not only a nonstoichiometric hydrate but also one that shows highly unusual characteristics in terms of gradual unit cell expansion and contraction despite the absence of continuous channels. These structural features in turn influence the tendency of this drug to convert to the more stable hemihydrate. The study has implications for the recognition and understanding of the behavior of pharmaceutical nonstoichiometric hydrates.