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 833.3nm) 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 833.3nm sizes was 1.69 and 2.59-fold higher than that for 16296.7nm system in dogs. To sum up, the critical particle size was found to be within the range of 833.3–4060.0nm (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.