Academic Journal
The amorphous state of the antiepileptic clobazam: preparation and characterization
| Τίτλος: | The amorphous state of the antiepileptic clobazam: preparation and characterization |
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| Συγγραφείς: | Marcos Valdez, Marina M., Sanchez, Julio, Bertotto, María E, Fandiño, Octavio E, Cometto, Fernando P., Sperandeo, Norma R. |
| Πηγή: | Marcos Valdez, M M, Sanchez, J, Bertotto, M E, Fandiño, O E, Cometto, F P & Sperandeo, N R 2025, 'The amorphous state of the antiepileptic clobazam: preparation and characterization', AAPS PharmSciTech, vol. 26, no. 5, 105. https://doi.org/10.1208/s12249-025-03101-y |
| Έτος έκδοσης: | 2025 |
| Συλλογή: | Queen's University Belfast: Research Portal |
| Θεματικοί όροι: | X-ray photoelectron spectroscopy, Clobazam, Humidity, Temperature, Anticonvulsants - chemistry, Photoelectron Spectroscopy - methods, 1,5-benzodiazepines, Thermogravimetry - methods, Transition Temperature, devitrification, Drug Stability, Spectroscopy, Fourier Transform Infrared - methods, dynamic mechanical analysis, Benzodiazepines - chemistry, X-Ray Diffraction - methods, Calorimetry, Differential Scanning - methods, conventional and modulated DSC, Chemistry, Pharmaceutical - methods, Crystallization - methods |
| Περιγραφή: | The aim of this study was to prepare and characterize amorphous clobazam (CLOB) and investigate its devitrification under various stressors (temperature/humidity, compaction and mechanical/thermal stresses). Amorphous CLOB was prepared by melt-quenching in liquid nitrogen. The quench-cooled sample (CLOB-q) was characterized via polarized light and hot-stage microscopies (PLM and HSM), X-ray powder diffraction (XRPD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), conventional and modulated DSC (DSC-c and MDSC®), thermogravimetry (TG), dynamic mechanical analysis (DMA), X-ray photoelectron spectroscopy (XPS) and contact angle measurements. Stability of CLOB-q toward temperature/humidity, compaction, and combined mechanical and thermal stress were also evaluated. CLOB-q was a truly amorphous form, as revealed by DSC-c, MDSC® and DMA. Its calorimetric glass transition temperature (Tg) was 67.0 °C (20 °C/min) and the ratio Tm/Tg was 1.34, indicating a fragile glass. The water contact angle of CLOB-q (121.8° ± 1.7°) was lower than that of crystalline CLOB (CLOB-c, 131.3° ± 3.6°), likely due to its higher concentration of surface CL, as determined by XPS. Storage of CLOB-q at - 20 °C/0% RH, 25 °C/0% RH and 40 °C/75% RH resulted in its complete devitrification to CLOB-c within 60 days, 4 days, and 42 h respectively. Subjection of CLOB-q to compaction (19.6 kN) and combined mechanical-thermal stresses also resulted in complete crystallization to CLOB-c. In conclusion, amorphous CLOB was successfully prepared in the laboratory for the first time and thoroughly characterized. It easily devitrified to CLOB-c by effect of different stressors, and thus it could not have advantages over CLOB-c in terms of physical stability. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | English |
| ISSN: | 1530-9932 |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/40244320; info:eu-repo/semantics/altIdentifier/pissn/1530-9932 |
| DOI: | 10.1208/s12249-025-03101-y |
| Διαθεσιμότητα: | https://pure.qub.ac.uk/en/publications/633bb828-6bc9-41a0-a16e-33834367759b https://doi.org/10.1208/s12249-025-03101-y |
| Rights: | info:eu-repo/semantics/closedAccess |
| Αριθμός Καταχώρησης: | edsbas.D23893E3 |
| Βάση Δεδομένων: | BASE |
| ISSN: | 15309932 |
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| DOI: | 10.1208/s12249-025-03101-y |