Study of the parameters influencing the co-grinding process for the production of meloxicam nanoparticles

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 dSEM = 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 °C), especially in the case of the amorphous product. Such dry powder systems can offer novel opportunities in systemic nasal drug delivery.