title: Dissolution study of nanocrystal powders of a poorly soluble drug by UV imaging and channel flow methods.
abstract: 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 (580 nm) 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.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland. Electronic address: annika.sarnes@helsinki.fi.
authors.forename: Annika
authors.initials: A
authors.lastname: Sarnes
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
authors.forename: Sabrine Smedegaard
authors.initials: SS
authors.lastname: Jensen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Aaltonen
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D004339:Drug Compounding; D004355:Drug Stability; D007213:Indomethacin / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D020442:Poloxamer / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011208:Powders; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
chemical_list: D011136:Polysorbates; D011208:Powders; D020442:Poloxamer; D007213:Indomethacin
keywords: Channel flow method; Dissolution rate; Nanocrystals; Poloxamer; Solubility; UV imaging