Thermal degradation of amorphous glibenclamide

Rehder, Sönke; Sakmann, Albrecht; Rades, Thomas; Leopold, Claudia

doi:10.1016/j.ejpb.2011.07.009

Cited by 22 publications

(14 citation statements)

References 11 publications

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“…In addition, a shoulder appeared at 1655 cm −1 , which can be attributed to CN stretching on an imidic acid tautomer of GBC. 30,41 These changes have been previously observed with amorphous GBC and suggest that the amide was converted predominantly into the imidic acid form upon amorphization. 41,42 The imidic acid structure is a thermodynamically less stable tautomer compared to the amide form; stabilization by intramolecular hydrogen bonding between the imidic acid and the aryl ether oxygen has been suggested.…”

Section: Resultssupporting

confidence: 69%

“…30,41 These changes have been previously observed with amorphous GBC and suggest that the amide was converted predominantly into the imidic acid form upon amorphization. 41,42 The imidic acid structure is a thermodynamically less stable tautomer compared to the amide form; stabilization by intramolecular hydrogen bonding between the imidic acid and the aryl ether oxygen has been suggested. 42,43 In Figure 3c, the spectra for crystalline LYS, crystalline SVS− LYS PM, and SVS−LYS CM are shown.…”

Section: Resultssupporting

confidence: 69%

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Amino Acids as Co-amorphous Excipients for Simvastatin and Glibenclamide: Physical Properties and Stability

et al. 2014

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Co-amorphous drug mixtures with low-molecular-weight excipients have recently been shown to be a promising approach for stabilization of amorphous drugs and thus to be an alternative to the traditional amorphous solid dispersion approach using polymers. However, the previous studies are limited to a few drugs and amino acids. To facilitate the rational selection of amino acids, the practical importance of the amino acid coming from the biological target site of the drug (and associated intermolecular interactions) needs to be established. In the present study, the formation of co-amorphous systems using cryomilling and combinations of two poorly water-soluble drugs (simvastatin and glibenclamide) with the amino acids aspartic acid, lysine, serine, and threonine was investigated. Solid-state characterization with X-ray powder diffraction, differential scanning calorimetry, and Fourier-transform infrared spectroscopy revealed that the 1:1 molar combinations simvastatin-lysine, glibenclamide-serine, and glibenclamide-threonine and the 1:1:1 molar combination glibenclamide-serine-threonine formed co-amorphous mixtures. These were homogeneous single-phase blends with weak intermolecular interactions in the mixtures. Interestingly, a favorable effect by the excipients on the tautomerism of amorphous glibenclamide in the co-amorphous blends was seen, as the formation of the thermodynamically less stable imidic acid tautomer of glibenclamide was suppressed compared to that of the pure amorphous drug. Furthermore, the co-amorphous mixtures provided a physical stability advantage over the amorphous drugs alone.

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Section: Resultssupporting

confidence: 69%

Section: Resultssupporting

confidence: 69%

Amino Acids as Co-amorphous Excipients for Simvastatin and Glibenclamide: Physical Properties and Stability

et al. 2014

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“…A peak corresponding to the melting and a baseline shift due to decomposition after melting were observed at 170 °C in the DSC curve of crystalline GLB (Figure 8a). 36,40 In amorphous GLB, a glass transition peak at 73 °C, a crystallization peak near 130 °C, and a melting peak of crystalline GLB around 170 °C and a baseline shift above ∼190 °C (decomposition of GLB) were observed (Figure 8c). In nano-A, a glass transition peak at 63 °C, a crystallization peak near 130 °C, and a melting peak of GLB crystal around 170 °C and a baseline shift above ∼190 °C (decomposition of GLB) were observed (Figure 8d).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Morphological and Physicochemical Evaluation of Two Distinct Glibenclamide/Hypromellose Amorphous Nanoparticles Prepared by the Antisolvent Method

et al. 2018

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The morphology and stability of amorphous nanoparticles of glibenclamide (GLB) prepared by the antisolvent method using different methods of adding hypromellose (HPMC) were evaluated. Nano-A was prepared by the injection of a dimethyl sulfoxide (DMSO) solution of GLB into the HPMC solution, whereas nano-B was obtained by the injection of a DMSO solution of GLB and HPMC into water. Cryogenic transmission electron microscopy, field-emission scanning electron microscopy, and field-emission transmission electron microscopy, including energy dispersive X-ray spectrometry, revealed that the particles of the nano-A and nano-B samples are hollow spheres and nonspherical nanoparticles, respectively. Powder X-ray diffraction and solid-state NMR measurements showed that GLB is present in an amorphous state in both nano-A and nano-B. The weight ratios of HPMC in the GLB/HPMC nanoparticles were 11 and 16% for nano-A and nano-B, respectively, as determined by solution-state NMR. The glass transition temperatures ( T) of nano-A and nano-B evaluated using differential scanning calorimetry were lower by about 10 °C compared to that of amorphous GLB, presumably because of a T confinement effect and the surface coverage and mixing of HPMC, as suggested by the inverse gas chromatography experiment. GLB crystallization during storage was suppressed more strongly in nano-B than nano-A, owing to the higher amount of HPMC and the higher miscibility between GLB and HPMC. It is suggested that the diffusion rate of the solvent during nanoprecipitation determined the nanoparticle properties. In nano-A, the precipitation of GLB first occurred at the outer interface because of the rapid diffusion of the solvent. Thus, hollow spherical particles with HPMC preferentially located near the surface were formed. On the other hand, the diffusion of the solvent in nano-B was suppressed because of the presence of HPMC, yielding small nonspherical nanoparticles with a high miscibility of GLB and HPMC.

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“…However, the DSC of GLB thin film indicated the GLB and PVP endothermic peaks at 172.80 and 122.61°C respectively, with slight decrease in the melting point (Figure 4). The observed slight decline in melting point and intensity of GLB endothermic peak of DSC thermo grams of thin film formulation might be partially attributed to the transformation of crystalline to amorphous drug or to the dissolution of drug in the carrier system at the temperatures below its melting point [49,50]. The broad endothermic peak ranging from 96.37-143.81°C might again be attributed due to the presence of residual moisture in PVP [51].…”

Section: Differential Scanning Calorimeter (Dsc)mentioning

confidence: 99%

Development and Evaluation of Polymer-bound Glibenclamide Oral Thin Film

G¹

2016

J Bioequiv Availab

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Thermal degradation of amorphous glibenclamide

Cited by 22 publications

References 11 publications

Amino Acids as Co-amorphous Excipients for Simvastatin and Glibenclamide: Physical Properties and Stability

Amino Acids as Co-amorphous Excipients for Simvastatin and Glibenclamide: Physical Properties and Stability

Morphological and Physicochemical Evaluation of Two Distinct Glibenclamide/Hypromellose Amorphous Nanoparticles Prepared by the Antisolvent Method

Development and Evaluation of Polymer-bound Glibenclamide Oral Thin Film

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