Preparation of cyclosporine A nanoparticles by evaporative precipitation into aqueous solution

Amorphous nanoparticle suspensions of a poorly water-soluble drug, cyclosporine A are produced by a new process, evaporative precipitation into aqueous solution (EPAS). The rapid evaporation of a heated organic solution of the drug, which is atomized into an aqueous solution, results in fast nucleation leading to nanoparticles suspensions. Hydrophilic stabilizers, introduced in the organic or aqueous phases, limit particle growth and inhibit crystallization for drug concentrations as high as 35 mg/ml, and drug/surfactant ratios up to 1.0. The suspensions may be used in parenteral formulations to enhance bioavailability or may be dried to produce oral dosage forms with the potential for high dissolution rates due to the low crystallinity, small particle size and hydrophilic stabilizer that enhances wetting. (C) 2002 Elsevier Science B.V. All rights reserved.