Journal
AICHE JOURNAL
Volume 52, Issue 7, Pages 2428-2435Publisher
WILEY
DOI: 10.1002/aic.10848
Keywords
ketoprofen; nanoparticle; precipitation; suspension; gel
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Aqueous nanoparticle gels of a poorly-water soluble drug, ketoprofen, were produced by evaporative precipitation into aqueous solution (EPAS). Liquid droplets of surfactant stabilized ketoprofen containing residual solvent were dispersed in water from 60 to 90 degrees C below the melting point of pure ketoprofen. The carboxylic acid group in ketoprofen dissociates in pure water, providing electrostatic stabilization of the droplets to complement steric stabilization. Stable amorphous ketoprofen particles with a mean size of 135 nm, measured by dynamic light scattering, were formed with only 0.1% w/v poloxamer 407, resulting in an exceptionally high drug-to-surfactant ratio of 10:1. For 5% w/v poloxamer 407, interactions with ketoprofen produced a bluish, transparent gel composed of similar to 50 nm particles. In 2 min, 98% of the ketoprofen in the gel nanoparticles dissolved The favorable interactions between the ketoprofen and poloxamer 407, along with the electrostatic and steric stabilization, lead to gelation, which further stabilizes the unusually small particles. The rapidly dissolving wet gels with extremely small particle sizes, one month stability, and relatively low viscosities, are of interest in transdermal and parenteral delivery; furthermore, the gels may be dried for oral delivery. (c) 2006 American Institute of Chemical Engineers.
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