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Titre du document / Document title

Crystallization and Crystallinity of Fluticasone Propionate

Auteur(s) / Author(s)

MURNANE Darragh (1) ; MARRIOTT Christopher (1) ; MARTIN Gary P. (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) King's College London, Drug Delivery Research Group, Pharmaceutical Sciences Division, 150 Stamford Street, London SE1 9NH, ROYAUME-UNI

Résumé / Abstract

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.

Revue / Journal Title

Crystal growth & design    ISSN  1528-7483 

Source / Source

2008, vol. 8, no8, pp. 2753-2764 [12 page(s) (article)] (56 ref.)

Langue / Language

Anglais

Editeur / Publisher

American Chemical Society, Washington,DC, ETATS-UNIS  (2001) (Revue)

Mots-clés anglais / English Keywords

Crystal growth from solutions

;

Fluticasone

;

Disordered crystals

;

Methanol

;

Ethylene oxide polymer

;

Mechanical alloying

;

Crystal structure

;

Polymorphism

;

Morphology

;

Ostwald ripening

;

Microcrystal

;

Nucleation

;

Solubility

;

Acetone

;

Polyethylene glycols

;

Aqueous solutions

;

Solubilization

;

Crystallinity

;

Crystallization

;

Mots-clés français / French Keywords

8110D

;

6460Q

;

6475

;

6470K

;

Croissance cristalline en solution

;

Fluticasone

;

Cristal désordonné

;

Méthanol

;

Ethylène oxyde polymère

;

Alliage mécanique

;

Structure cristalline

;

Polymorphisme

;

Morphologie

;

Maturation Ostwald

;

Microcristal

;

Nucléation

;

Solubilité

;

Acétone

;

Ethylène oxyde polymère

;

Solution aqueuse

;

Solubilisation

;

Cristallinité

;

Cristallisation

;

Mots-clés espagnols / Spanish Keywords

Fluticasona

;

Cristal desordenado

;

Etileno óxido polímero

;

Maduración Ostwald

;

Microcristal

;

Solubilización

;

Cristalinidad

;

Localisation / Location

INIST-CNRS, Cote INIST : 27261, 35400019744631.0330

Nº notice refdoc (ud4) : 20577346



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