Dissolution study of nanocrystal powders of a poorly soluble drug by UV imaging and channel flow methods

[Display omitted] Application of drug nanocrystals provides advantageous options for the pharmaceutical formulation development of poorly soluble drugs. The objective of this study was to investigate the dissolution behavior improving effects of differently sized nanocrystals of a poorly soluble mod...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2013-11, Vol.50 (3-4), p.511-519
Main Authors: Sarnes, Annika, Østergaard, Jesper, Jensen, Sabrine Smedegaard, Aaltonen, Jaakko, Rantanen, Jukka, Hirvonen, Jouni, Peltonen, Leena
Format: Article
Language:English
Subjects:
Channel flow method
Dissolution rate
Drug Compounding
Drug Stability
Indomethacin - chemistry
Microscopy, Electron, Scanning
Nanocrystals
Nanoparticles - chemistry
Nanoparticles - ultrastructure
Poloxamer
Poloxamer - chemistry
Polysorbates - chemistry
Powders
Solubility
Spectrophotometry, Ultraviolet
UV imaging
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Summary:[Display omitted] Application of drug nanocrystals provides advantageous options for the pharmaceutical formulation development of poorly soluble drugs. The objective of this study was to investigate the dissolution behavior improving effects of differently sized nanocrystals of a poorly soluble model drug, indomethacin. Nanocrystal suspensions were prepared using a top-down wet milling technique with three stabilizers: poloxamer F68, poloxamer F127 and polysorbate 80. The dissolution of the differently sized indomethacin nanocrystals were investigated using a channel flow dissolution method and by UV imaging. Unmilled bulk indomethacin and physical mixtures were used as references. According to both the dissolution methods, the dissolution properties of indomethacin were improved by the particle size reduction. UV imaging was used for the first time as a dissolution testing method for fast dissolving nanoscale material. The technique provided new information about the concentration of the dissolved drug next to the sample surface; with the smallest nanocrystals (580nm) the indomethacin concentration next to the particle surface exceeded five-fold the thermodynamic saturated indomethacin solution concentration. Thus the solubility improvement itself, not only the increased surface area for dissolution, may have an important role in the higher dissolution rates of nanocrystal formulations. Poloxamer F68 was the most optimal stabilizer in the preparation of the indomethacin nanocrystal suspensions and in the solubility and dissolution enhancement as well.
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2013.08.030