title: Relationship between dissolution and bioavailability for nimodipine colloidal dispersions: the critical size in improving bioavailability.
abstract: To compare the dissolution and bioavailability for nimodipine microcrystals and nanocrystals, and to determine the critical size range in improving the oral absorption of nimodipine. Nimodipine microcrystals and nanocrystals were prepared using a microprecipitation method. The particle size was determined with a laser diffraction method. X-ray powder diffraction was applied to inspect the potential crystal form transition. The aqueous solubility was determined by shaking flasks, and the dissolution behavior was evaluated using the paddle method. The pharmacokinetics was performed in beagle dogs in a crossover experimental design. Three nimodipine colloidal dispersions (16296.7, 4060.0 and 833.3 nm) were prepared, respectively. Nimodipine had undergone crystal form transition during microprecipitation process, but experienced no conversion under the high-pressure homogenization. The colloidal dispersions did not show any difference in aqueous equilibrium solubility. Additionally, the three formulations also displayed similar dissolution curves in purified water and 0.05% SDS. The AUC for dispersions of 4060.0 and 833.3 nm sizes was 1.69 and 2.59-fold higher than that for 16296.7 nm system in dogs. To sum up, the critical particle size was found to be within the range of 833.3-4060.0 nm (average volume-weighted particle size) in improving the bioavailability of nimodipine, and dissolution performance was not an effective index in evaluating the bioavailability for nimodipine colloidal dispersions.
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Longfa
authors.initials: L
authors.lastname: Kou
authors.forename: Cheng
authors.initials: C
authors.lastname: Gong
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Meina
authors.initials: M
authors.lastname: Liu
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Sui
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003102:Colloids; D003460:Crystallization; D004285:Dogs; D008297:Male; D053758:Nanoparticles; D009553:Nimodipine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D002121:Calcium Channel Blockers; D003102:Colloids; D009553:Nimodipine