title: Preparation and evaluation of high dispersion stable nanocrystal formulation of poorly water-soluble compounds by using povacoat.
abstract: In this study, we reported the application of Povacoat®, a hydrophilic polyvinylalcohol copolymer, as a dispersion stabilizer of nanoparticles of poorly water-soluble compounds. In addition, the influence of aggregation of the nanoparticles on their solubility and oral absorption was studied. Griseofulvin (GF) was used as a model compound with poor water solubility and was milled to nanoparticles by wet bead milling. The dispersion stability of GF milled with Povacoat® or the generally used polymers (polyvinylalcohol, hydroxypropylcellulose SSL, and polyvinylpyrrolidone K30) was compared. Milled GF suspended in Povacoat® aqueous solution with D-mannitol, added to improve the disintegration rate of freeze-dried GF, exhibited high dispersion stability without aggregation (D90 = ca. 0.220 μm), whereas milled GF suspended in aqueous solutions of the other polymers aggregated (D90 > 5 μm). Milled GF with Povacoat® showed improved aqueous solubility and bioavailability compared with the other polymers. The aggregation of nanoparticles had significant impact on the solubility and bioavailability of GF. Povacoat® also prevented the aggregation of the various milled poorly water-soluble compounds (hydrochlorothiazide and tolbutamide, etc.) more effectively than the other polymers. These results showed that Povacoat® could have wide applicability to the development of nanoformulations of poorly water-soluble compounds.
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan. Electronic address: yuminoki@pharm.setsunan.ac.jp.
authors.forename: Kayo
authors.initials: K
authors.lastname: Yuminoki
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
authors.forename: Fuko
authors.initials: F
authors.lastname: Seko
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Horii
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Teramoto
authors.affiliation: Quality Management Group, Quality Compliance Division, Santen Pharmaceutical Company Ltd., Kita-ku, Osaka 530-8552, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nakada
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Hashimoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D006118:Griseofulvin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008297:Male; D008353:Mannitol / Q000737:chemistry; D053758:Nanoparticles; D036103:Nanotechnology; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000031:analogs & derivatives / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D005079:Excipients; D006118:Griseofulvin; D008353:Mannitol; D011142:Polyvinyl Alcohol; D002482:Cellulose; D019904:Polymethyl Methacrylate; C008079:hydroxypropylcellulose; D011205:Povidone
keywords: freeze-drying: oral absorption; milling; nanoparticles; nanotechnology; polymers; poorly water-soluble drugs