Micronization of meloxicam using a supercritical fluids process

A pre-filtration rapid expansion of a supercritical solution (PF-RESS) technique was developed to reduce particle size and to increase drug solubility. Carbon dioxide was used as the supercritical fluid and meloxicam was employed as the model drug. The meloxicam content was measured using high-performance liquid chromatography (HPLC). The physicochemical properties of the micronized meloxicam, were assessed using scanning electron and optical microscopy, laser light scattering, and powder X-ray diffraction. No aggregation occurred and no polymorphism was observed in the micronized drug. The morphology of the micronized drug was irregular in shape, with a uniform particle size between 0.5 and 2 mu m. The micronized meloxicam solubility in water (7.9 mu g/mL) and the solubility rate (0.19 mu g/mL/min) after a period of 30 min were faster than non-micronized meloxicam (3.6 mu g/mL and 0.02 mu g/mL/min, respectively). Although no significant change in dissolution rate at pH 1.2 was observed between the micronized and non-micronized meloxicam, when the pH was increased to 5.0-7.4, the micronized meloxicam showed a significant increase in dissolution rate after a period of 180 min. Our results provide an alternative methodology for improving the solubility of poorly soluble drugs, and show this methodology's great potential in oral drug delivery systems. (c) 2007 Elsevier B.V. All rights reserved.