Different or the same? exploring the physicochemical properties and molecular mobility of celecoxib amorphous forms.

Autor: Wang M; School of Pharmacy, Henan University, Kaifeng, China; Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark; State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, China., Aalling-Frederiksen O; Department of Chemistry and Nano-Science Center, University of Copenhagen, Copenhagen, Denmark., Madsen AØ; Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark., Jensen KMØ; Department of Chemistry and Nano-Science Center, University of Copenhagen, Copenhagen, Denmark., Jørgensen MRV; Department of Chemistry & iNANO, Aarhus University, Aarhus, Denmark; MAX IV Laboratory, Lund University, Lund, Sweden., Gong J; State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, China., Rades T; Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark. Electronic address: thomas.rades@sund.ku.dk., Martins ICB; Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark. Electronic address: ines.martins@sund.ku.dk.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Aug 15; Vol. 661, pp. 124470. Date of Electronic Publication: 2024 Jul 14.
DOI: 10.1016/j.ijpharm.2024.124470
Abstrakt: The influence of different preparation methods on the physicochemical properties of amorphous solid forms have gained considerable attention, especially with recent publications on pharmaceutical polyamorphism. In the present study, we have investigated the possible occurrence of polyamorphism in the drug celecoxib (CEL) by investigating the thermal behavior, morphology, structure, molecular mobility and physical stability of amorphous CEL obtained by quench-cooling (QC), ball milling (BM) and spray drying (SD). Similar glass transition temperatures but different recrystallization behaviors were observed for CEL-QC, CEL-BM and CEL-SD using modulated differential scanning calorimetry analysis. A correlation between the different recrystallization behaviors of the three CEL amorphous forms and the respective distinct powder morphologies, was also found. Molecular dynamics simulations however, reveal that CEL presents similar molecular conformational distributions when subjected to QC and SD. Moreover, the obtained molecular conformational distributions of CEL are different from the ones found in its crystal structure and also from the ones found in the lowest-energy structure obtained by quantum mechanical calculations. The type and strength of CEL hydrogen bond interactions found in CEL-QC and CEL-SD systems are almost identical, though different from the ones presented in the crystal structure. Pair distribution function analyses and isothermal microcalorimetry show similar local structures and structural relaxation times, respectively, for CEL-QC, CEL-BM and CEL-SD. The present work shows that not only similar physicochemical properties (glass transition temperature, and structural relaxation time), but also similar molecular conformational distributions were observed for all prepared CEL amorphous systems. Hence, despite their different recrystallization behaviors, the three amorphous forms of CEL did not show any signs of polyamorphism.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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