Effects of excipient formulation on the morphology and aqueous re-dispersibility of dry-powder silica nano-aggregates

Dry-powder aggregates of biocompatible silica nanoparticles are manufactured by the spray-drying technique to be potentially developed as an inhaled drug delivery vehicle. The micron-scale nano-aggregates are specifically designed to exhibit large, hollow, and spherical morphologies in order to achieve high aerosolization efficiency and an effective deposition in the lung. In addition to the specific morphology, the dry-powder nano-aggregates must readily re-disperse into the primary nanoparticles in an aqueous medium to be therapeutically effective. The presence of water-soluble excipients that form "excipient bridges" interconnecting the silica nanoparticles is found to be critical in the nano-aggregate re-dispersion process. The effects of different excipient formulations on the nano-aggregate morphology and aqueous re-dispersibility are therefore examined. Three of the most widely used excipients in inhaled drug delivery formulations (i.e. leucine, mannitol, and lactose) are employed as the excipient candidates. The nano-aggregate morphology and the aqueous re-dispersibility are found to be highly influenced by the excipient type, in particular its hydrophilicity, and the nanoparticle to excipient concentration ratio. A multiple-excipient formulation of leucine and lactose at a 1:6 concentration ratio is found to produce nano-aggregates having both the desired morphology and excellent aqueous re-dispersibility. (C) 2010 Elsevier B.V. All rights reserved.