Co-grinding is a procedure for the preparation of nanoparticles in which the drug is ground together with one or more excipients. The grinding of meloxicam, a crystalline solid, together with amorphous polyvinylpyrrolidone (PVP) or semi-crystalline polyethylene glycol (PEG) as excipients, is expected to lead to a drastic reduction in particle size. We optimized meloxicam grinding using a three level full factorial response surface design. In the case of PVP the optimum co-grinding parameter set in our study proved to be a meloxicam to PVP-C30 ratio of 1:1, and a rotation frequency of 400 rpm. The best size reduction was achieved at a meloxicam to PEG 6000 ratio = 1:2 at a rotation frequency of 400 rpm: nanoparticles averaging d(SEM) = 174 nm in diameter and with a very narrow size distribution (standard deviation 35% of mean) were obtained. X-ray powder diffraction analysis indicated that the optimized products contained amorphous meloxicam nanoparticles in the PVP-C30 composition, although meloxicam nanocrystals could also be detected in the samples which contained PEG 6000. The dissolution properties were significantly increased under nasal conditions (pH 5.1, temperature 30 degrees C), especially in the case of the amorphous product. Such dry powder systems can offer novel opportunities in systemic nasal drug delivery. (C) 2011 Elsevier B.V. All rights reserved.