title: Enhancement of amorphous celecoxib stability by mixing it with octaacetylmaltose: the molecular dynamics study.
abstract: In this paper, we present a novel way of stabilization of amorphous celecoxib (CEL) against recrystallization by preparing binary amorphous celecoxib-octaacetylmaltose (CEL-acMAL) systems by quench-cooling of the molten phase. As far as we know this is the first application of carbohydrate derivatives with acetate groups to enhance the stability of an amorphous drug. We found that CEL in the amorphous mixture with acMAL is characterized by a much better solubility than pure CEL. We report very promising results of the long-term measurements of stability of the CEL-acMAL binary amorphous system with small amount of stabilizer during its storage at room temperature. Moreover, we examined the effect of adding acMAL on molecular dynamics of CEL in the wide temperature range in both the supercooled liquid and glassy states. We found that the molecular mobility of the mixture of CEL with 10 wt % acMAL in the glassy state is much more limited than that in the case of pure CEL, which correlates with the better stability of the amorphous binary system. By dielectric measurements and theoretical calculations within the framework of density functional theory (DFT), we studied the role of acMAL in enhancing the stability of amorphous CEL in mixtures and postulated which interactions between CEL and acMAL molecules can be responsible for preventing devitrification.
authors.affiliation: Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland. katarzyna.grzybowska@us.edu.pl
authors.forename: K
authors.initials: K
authors.lastname: Grzybowska
authors.forename: M
authors.initials: M
authors.lastname: Paluch
authors.forename: P
authors.initials: P
authors.lastname: Wlodarczyk
authors.forename: A
authors.initials: A
authors.lastname: Grzybowski
authors.forename: K
authors.initials: K
authors.lastname: Kaminski
authors.forename: L
authors.initials: L
authors.lastname: Hawelek
authors.forename: D
authors.initials: D
authors.lastname: Zakowiecki
authors.forename: A
authors.initials: A
authors.lastname: Kasprzycka
authors.forename: I
authors.initials: I
authors.lastname: Jankowska-Sumara
mesh_terms: D000068579:Celecoxib; D004355:Drug Stability; D008320:Maltose / Q000031:analogs & derivatives* / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011720:Pyrazoles / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D008320:Maltose; D000068579:Celecoxib