title: Buserelin acetate microparticle dispersion effects drug release and plasma E(1) levels.
abstract: We investigated the effect of different dispersion methods on release behavior and efficacy onset following microparticle administration of buserelin acetate (BA) sustained-release injection. In this in vitro release study, the initial dispersion of BA increased with increased stirring speed (p<0.01). Stability of BA was studied over 7 days after BA release. The initial BA release rate was higher (p<0.01) after a 1-min vibration dispersion method (VDM) using a test tube mixer (2000 rpm) compared with the standard dispersion method (SDM) by hand. Without shaking, powder aggregation was observed, and BA release was lower than in either the SDM or VDM methods. In this study using 4-week-old Sprague-Dawley female rats, the initial plasma estrone (E(1)) concentrations were lower (p<0.05) in the VDM method than in the SDM method. Observations by optical microscope and scanning microscope showed no change in microparticle shape or distribution of size induced by SDM, VDM or the ultrasonication dispersion method. These results suggest that different dispersion methods do not change the shape and distribution of microparticle size, but clearly change the BA release rate and the transition in plasma E(1) concentrations that can affect drug efficacy.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsuruma, Showa-ku, Nagoya, Aichi 466-8560, Japan. Makiko.Usami@sanofi-aventis.com
authors.forename: Makiko
authors.initials: M
authors.lastname: Usami
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Misawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Yagi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sekikawa
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D000818:Animals; D002064:Buserelin / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D015536:Down-Regulation; D004970:Estrone / Q000097:blood*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D004970:Estrone; D007987:Gonadotropin-Releasing Hormone; D002064:Buserelin