Détail de la notice
Titre du Document
Crystallization and Crystallinity of Fluticasone Propionate
Auteur(s)
MURNANE Darragh ; MARRIOTT Christopher ; MARTIN Gary P.
Résumé
Solubilization of fluticasone propionate (FP) was effected using aqueous solutions of (i) different grades of poly(ethylene glycol) (PEG), (ii) methanol, and (iii) acetone to enable antisolvent crystallization by the addition of water. The solubility of FP in acetone was significantly higher than in PEG 400 or PEG 6000, and FP solubility was observed to be nonideal in either cosolvent. Crystallization of FP was instantaneous upon addition of water as antisolvent, with nucleation occurring during the mixing phase. The smallest crystals were produced in all cases from PEG solvents, which was attributed to a greater degree of nucleation and microcrystals of a size-range were produced. Crystals produced from PEG solvents also displayed a resistance to agglomeration and Ostwald ripening, which was observed to affect the morphology of FP crystallized from either methanol or acetone by the addition of water. In spite of the very rapid kinetics of solid formation, FP crystallized as the stable Form I polymorph from PEG 400 and PEG 6000. Conversely, mechanical milling of highly crystalline particles resulted in the generation of disorder in the crystals, which was apparent from surface dynamic vapor sorption analysis. The generation of FP microcrystals with a small size range from environmentally benign PEG solvents as the stable crystalline form represents an improvement over current crystallization and micronization techniques for the production of inhalable FP.
Editeur
American Chemical Society
Identifiant
ISSN : 1528-7483
Source
Crystal growth & design A. 2008, vol. 8, n° 8, pp. 2753-2764 [12 pages] [bibl. : 56 ref.]
Langue
Anglais
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