Journal
JOURNAL OF SUPERCRITICAL FLUIDS
Volume 88, Issue -, Pages 56-65Publisher
ELSEVIER
DOI: 10.1016/j.supflu.2014.01.015
Keywords
Diflunisal; dissolution rate enhancement; drug-polymer interaction; polyvinylpyrrolidone; supercritical antisolvent
Categories
Funding
- Spanish Ministry of Science and Innovation (MICINN)
- Erasmus Mundus University II predoctoral grant
- [CTQ2010-16940]
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Dissolution rate enhancement of the anti-inflammatory drug diflunisal was achieved using for the first time a supercritical fluid technology. The supercritical fluid antisolvent (SAS) method was applied to precipitate diflunisal alone and to coprecipitate the drug together with the biocompatible polymer polyvinylpyrrolidone (PVP K-30 and K-10). The untreated and SAS processed diflunisal, and the coprecipitates were characterized in terms of size, morphology, crystallinity, compositions, drug-polymer interactions, and drug release. SAS processed diflunisal exhibited a polymorphic form different from that of the untreated drug. Diflunisal crystallinity disappeared in the coprecipitates. Three different drug: polymer mass ratios were studied: 75:25, 50:50, and 25:75. Microparticle size decreased and aggregation disappeared as the relative amount of polymer increased. The 25:75 coprecipitate consisted of loose spherical particles exhibiting mean particle size of 410 nm while the 75:25 coprecipitate consisted of bigger aggregated particles. The SAS method was shown to be a suitable technology to form solid dispersions of a poorly soluble drug. (C) 2014 Elsevier B.V. All rights reserved.
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